Modification of chemokine pathways and immune cell infiltration as a novel therapeutic approach in liver inflammation and fibrosis

Inflammation and Allergy - Drug Targets

Volumn 10, Issue 6, 2011, Pages 509-536

  Zimmermann, Henning W ^a   Tacke, Frank ^a  

^a UNIVERSITY HOSPITAL RWTH AACHEN   (Germany)

Author keywords

Animal models; Chemokines; Human studies; Inflammation; Liver cirrhosis; Liver fibrosis; Macrophage; Monocyte; T cells

Indexed keywords

CCL1 CHEMOKINE; CHEMOKINE; CHEMOKINE RECEPTOR CCR1; CHEMOKINE RECEPTOR CCR2; CHEMOKINE RECEPTOR CCR5; COLLAGEN; CUTANEOUS T CELL ATTRACTING CHEMOKINE; CXCL1 CHEMOKINE; CXCL11 CHEMOKINE; CXCL2 CHEMOKINE; CXCL9 CHEMOKINE; EOTAXIN; EOTAXIN 2; EOTAXIN 3; EPITHELIAL DERIVED NEUTROPHIL ACTIVATING FACTOR 78; GAMMA INTERFERON INDUCIBLE PROTEIN 10; GRANULOCYTE CHEMOTACTIC PROTEIN 2; INTERLEUKIN 13; INTERLEUKIN 4; INTERLEUKIN 8; MACROPHAGE INFLAMMATORY PROTEIN 1ALPHA; MACROPHAGE INFLAMMATORY PROTEIN 1BETA; MACROPHAGE INFLAMMATORY PROTEIN 3ALPHA; MONOCYTE CHEMOTACTIC PROTEIN 1; MONOCYTE CHEMOTACTIC PROTEIN 2; MONOCYTE CHEMOTACTIC PROTEIN 3; MONOCYTE CHEMOTACTIC PROTEIN 4; RANTES; STROMAL CELL DERIVED FACTOR 1; UNINDEXED DRUG;

CELL INFILTRATION; CELL LINEAGE; CELL MIGRATION; CELL POPULATION; CHRONIC LIVER DISEASE; EXTRACELLULAR MATRIX; HEPATITIS; HEPATITIS C; HUMAN; IMMUNOCOMPETENT CELL; LIVER FIBROSIS; LIVER SINUSOID; MACROPHAGE; MONOCYTE; MONONUCLEAR CELL; NATURAL KILLER T CELL; NONALCOHOLIC FATTY LIVER; NONHUMAN; REVIEW; SCAR FORMATION; STELLATE CELL; T LYMPHOCYTE SUBPOPULATION;

EID: 81155123815     PISSN: 18715281     EISSN: None     Source Type: Journal    
DOI: 10.2174/187152811798104890     Document Type: Review

References (278)

1. Tsochatzis, E. A.; Bosch, J.; Burroughs, A. K. Prolonging survival in patients with cirrhosis: old drugs with new indications. Gastroenterology, 2010, 139 (6), 1813-1815 e1.
2. Schuppan, D.; Afdhal, N. H. Liver cirrhosis. Lancet 2008, 371 (9615), 838-51.
3. Wallace, K.; Burt, A. D.; Wright, M. C. Liver fibrosis. Biochem. J., 2008, 411 (1), 1-18.
4. Wynn, T. A. Cellular and molecular mechanisms of fibrosis. J. Pathol., 2008, 214 (2), 199-210.
5. Henderson, N. C.; Iredale, J. P. Liver fibrosis: cellular mechanisms of progression and resolution. Clin. Sci. (Lond), 2007, 112 (5), 265-280.
6. Chang, T. T.; Liaw, Y. F.; Wu, S. S.; Schiff, E.; Han, K. H.; Lai, C. L.; Safadi, R.; Lee, S. S.; Halota, W.; Goodman, Z.; Chi, Y. C.; Zhang, H.; Hindes, R.; Iloeje, U.; Beebe, S.; Kreter, B. Long-term entecavir therapy results in the reversal of fibrosis/cirrhosis and continued histological improvement in patients with chronic hepatitis B. Hepatology, 2010, 52 (3), 886-893.
7. Wasmuth, H. E.; Tacke, F.; Trautwein, C. Chemokines in liver inflammation and fibrosis. Semin. Liver Dis., 2010, 30 (3), 215-225.
8. Limmer, A.; Ohl, J.; Kurts, C.; Ljunggren, H. G.; Reiss, Y.; Groettrup, M.; Momburg, F.; Arnold, B.; Knolle, P. A. Efficient presentation of exogenous antigen by liver endothelial cells to CD8+ T cells results in antigen-specific T-cell tolerance. Nat. Med., 2000, 6 (12), 1348-1354.
9. Racanelli, V.; Rehermann, B. The liver as an immunological organ. Hepatology, 2006, 43 (2 Suppl 1), S54-62.
10. Ichikawa, S.; Mucida, D.; Tyznik, A. J.; Kronenberg, M.; Cheroutre, H. Hepatic stellate cells function as regulatory bystanders. J. Immunol., 2011, 186 (10), 5549-5555.
11. Winau, F.; Hegasy, G.; Weiskirchen, R.; Weber, S.; Cassan, C.; Sieling, P. A.; Modlin, R. L.; Liblau, R. S.; Gressner, A. M.; Kaufmann, S. H. Ito cells are liver-resident antigen-presenting cells for activating T cell responses. Immunity, 2007, 26 (1), 117-129.
12. Friedman, S. L. Mechanisms of hepatic fibrogenesis. Gastroenterology, 2008, 134 (6), 1655-1669.
13. Heymann, F.; Trautwein, C.; Tacke, F. Monocytes and macrophages as cellular targets in liver fibrosis. Inflamm. Allergy Drug Targets, 2009, 8 (4), 307-318.
14. Bataller, R.; Brenner, D. A. Liver fibrosis. J. Clin. Invest., 2005, 115 (2), 209-218.
15. Tacke, F.; Luedde, T.; Trautwein, C. Inflammatory pathways in liver homeostasis and liver injury. Clin. Rev. Allergy Immunol., 2009, 36 (1), 4-12.
16. Snowdon, V. K.; Fallowfield, J. A. Models and mechanisms of fibrosis resolution. Alcohol. Clin. Exp. Res., 2011, 35 (5), 794-799.
17. Zlotnik, A.; Yoshie, O. Chemokines: a new classification system and their role in immunity. Immunity, 2000, 12 (2), 121-127.
18. Mellado, M.; Rodriguez-Frade, J. M.; Manes, S.; Martinez, A. C. Chemokine signaling and functional responses: the role of receptor dimerization and TK pathway activation. Annu. Rev. Immunol., 2001, 19, 397-421.
19. Oo, Y. H.; Shetty, S.; Adams, D. H. The role of chemokines in the recruitment of lymphocytes to the liver. Dig. Dis., 2010, 28 (1), 31-44.
20. Schall, T. J.; Proudfoot, A. E. Overcoming hurdles in developing successful drugs targeting chemokine receptors. Nat. Rev. Immunol., 2011, 11 (5), 355-363.
21. Mantovani, A.; Cassatella, M. A.; Costantini, C.; Jaillon, S. Neutrophils in the activation and regulation of innate and adaptive immunity. Nat. Rev. Immunol., 2011, 11 (8), 519-531.
22. Bautista, A. P. Neutrophilic infiltration in alcoholic hepatitis. Alcohol, 2002, 27 (1), 17-21.
23. Ramaiah, S.; Rivera, C.; Arteel, G. Early-phase alcoholic liver disease: an update on animal models, pathology, and pathogenesis. Int. J. Toxicol., 2004, 23 (4), 217-231.
24. Bonder, C. S.; Ajuebor, M. N.; Zbytnuik, L. D.; Kubes, P.; Swain, M. G. Essential role for neutrophil recruitment to the liver in concanavalin A-induced hepatitis. J. Immunol., 2004, 172 (1), 45-53.
25. Jaeschke, H.; Farhood, A.; Smith, C. W. Neutrophils contribute to ischemia/reperfusion injury in rat liver in vivo. FASEB J., 1990, 4 (15), 3355-3359.
26. Liu, Z. X.; Han, D.; Gunawan, B.; Kaplowitz, N. Neutrophil depletion protects against murine acetaminophen hepatotoxicity. Hepatology, 2006, 43 (6), 1220-1230.
27. Saito, J. M.; Maher, J. J. Bile duct ligation in rats induces biliary expression of cytokine-induced neutrophil chemoattractant. Gastroenterology, 2000, 118 (6), 1157-1168.
28. Hill, D. A.; Jean, P. A.; Roth, R. A. Bile duct epithelial cells exposed to alpha-naphthylisothiocyanate produce a factor that causes neutrophil-dependent hepatocellular injury in vitro. Toxicol. Sci., 1999, 47 (1), 118-125.
29. Ramaiah, S. K.; Jaeschke, H. Role of neutrophils in the pathogenesis of acute inflammatory liver injury. Toxicol. Pathol., 2007, 35 (6), 757-766.
30. Lawson, J. A.; Fisher, M. A.; Simmons, C. A.; Farhood, A.; Jaeschke, H. Parenchymal cell apoptosis as a signal for sinusoidal sequestration and transendothelial migration of neutrophils in murine models of endotoxin and Fas-antibody-induced liver injury. Hepatology, 1998, 28 (3), 761-767.
31. Jaeschke, H.; Fisher, M. A.; Lawson, J. A.; Simmons, C. A.; Farhood, A.; Jones, D. A. Activation of caspase 3 (CPP32)-like proteases is essential for TNF-alpha-induced hepatic parenchymal cell apoptosis and neutrophil-mediated necrosis in a murine endotoxin shock model. J. Immunol., 1998, 160 (7), 3480-3486.
32. Bajt, M. L.; Farhood, A.; Jaeschke, H. Effects of CXC chemokines on neutrophil activation and sequestration in hepatic vasculature. Am. J. Physiol. Gastrointest. Liver Physiol., 2001, 281 (5), G1188-1195.
33. Okaya, T.; Lentsch, A. B. Cytokine cascades and the hepatic inflammatory response to ischemia and reperfusion. J. Invest. Surg., 2003, 16 (3), 141-147.
34. Clarke, C.; Kuboki, S.; Sakai, N.; Kasten, K. R.; Tevar, A. D.; Schuster, R.; Blanchard, J.; Caldwell, C. C.; Edwards, M. J.; Lentsch, A. B. CXC chemokine receptor-1 is expressed by hepatocytes and regulates liver recovery after hepatic ischemia/reperfusion injury. Hepatology, 2011, 53 (1), 261-271.
35. Jaeschke, H. Mechanisms of Liver Injury. II. Mechanisms of neutrophil-induced liver cell injury during hepatic ischemia-reperfusion and other acute inflammatory conditions. Am. J. Physiol. Gastrointest. Liver Physiol., 2006, 290 (6), G1083-1088.
36. Sheron, N.; Bird, G.; Koskinas, J.; Portmann, B.; Ceska, M.; Lindley, I.; Williams, R. Circulating and tissue levels of the neutrophil chemotaxin interleukin-8 are elevated in severe acute alcoholic hepatitis, and tissue levels correlate with neutrophil infiltration. Hepatology, 1993, 18 (1), 41-46.
37. Maher, J. J.; Scott, M. K.; Saito, J. M.; Burton, M. C. Adenovirus-mediated expression of cytokine-induced neutrophil chemoattractant in rat liver induces a neutrophilic hepatitis. Hepatology, 1997, 25 (3), 624-630.
38. Colletti, L. M.; Kunkel, S. L.; Walz, A.; Burdick, M. D.; Kunkel, R. G.; Wilke, C. A.; Strieter, R. M. The role of cytokine networks in the local liver injury following hepatic ischemia/reperfusion in the rat. Hepatology, 1996, 23 (3), 506-514.
39. Lentsch, A. B.; Yoshidome, H.; Cheadle, W. G.; Miller, F. N.; Edwards, M. J. Chemokine involvement in hepatic ischemia/reperfusion injury in mice: roles for macrophage inflammatory protein-2 and KC. Hepatology, 1998, 27 (4), 1172-1177.
40. Van Lint, P.; Wielockx, B.; Puimege, L.; Noel, A.; Lopez-Otin, C.; Libert, C. Resistance of collagenase-2 (matrix metalloproteinase-8)-deficient mice to TNF-induced lethal hepatitis. J. Immunol., 2005, 175 (11), 7642-7649.
41. Cavalieri, B.; Mosca, M.; Ramadori, P.; Perrelli, M. G.; De Simone, L.; Colotta, F.; Bertini, R.; Poli, G.; Cutrin, J. C. Neutrophil recruitment in the reperfused-injured rat liver was effectively attenuated by repertaxin, a novel allosteric noncompetitive inhibitor of CXCL8 receptors: a therapeutic approach for the treatment of post-ischemic hepatic syndromes. Int. J. Immunopathol. Pharmacol., 2005, 18 (3), 475-486.
42. Bertini, R.; Allegretti, M.; Bizzarri, C.; Moriconi, A.; Locati, M.; Zampella, G.; Cervellera, M. N.; Di Cioccio, V.; Cesta, M. C.; Galliera, E.; Martinez, F. O.; Di Bitondo, R.; Troiani, G.; Sabbatini, V.; D'Anniballe, G.; Anacardio, R.; Cutrin, J. C.; Cavalieri, B.; Mainiero, F.; Strippoli, R.; Villa, P.; Di Girolamo, M.; Martin, F.; Gentile, M.; Santoni, A.; Corda, D.; Poli, G.; Mantovani, A.; Ghezzi, P.; Colotta, F. Noncompetitive allosteric inhibitors of the inflammatory chemokine receptors CXCR1 and CXCR2: prevention of reperfusion injury. Proc. Natl. Acad. Sci. USA, 2004, 101 (32), 11791-1176.
43. Sakai, N.; Kuboki, S.; Van Sweringen, H. L.; Tevar, A. D.; Schuster, R.; Blanchard, J.; Edwards, M. J.; Lentsch, A. B. CXCR1 deficiency does not alter liver regeneration after partial hepatectomy in mice. Transplant. Proc., 2011, 43 (5), 1967-1970.
44. Mosher, B.; Dean, R.; Harkema, J.; Remick, D.; Palma, J.; Crockett, E. Inhibition of Kupffer cells reduced CXC chemokine production and liver injury. J. Surg. Res., 2001, 99 (2), 201-210.
45. Xu, J.; Lee, G.; Wang, H.; Vierling, J. M.; Maher, J. J. Limited role for CXC chemokines in the pathogenesis of alpha-naphthylisothiocyanate-induced liver injury. Am. J. Physiol. Gastrointest. Liver Physiol., 2004, 287 (3), G734-41.
46. Dorman, R. B.; Gujral, J. S.; Bajt, M. L.; Farhood, A.; Jaeschke, H. Generation and functional significance of CXC chemokines for neutrophil-induced liver injury during endotoxemia. Am. J. Physiol. Gastrointest. Liver Physiol., 2005, 288 (5), G880-6.
47. Stefanovic, L.; Brenner, D. A.; Stefanovic, B. Direct hepatotoxic effect of KC chemokine in the liver without infiltration of neutrophils. Exp. Biol. Med. (Maywood), 2005, 230 (8), 573-586.
48. Stefanovic, L.; Stefanovic, B. Mechanism of direct hepatotoxic effect of KC chemokine: sequential activation of gene expression and progression from inflammation to necrosis. J. Interferon. Cytokine Res., 2006, 26 (10), 760-770.
49. Dominguez, M.; Miquel, R.; Colmenero, J.; Moreno, M.; Garcia-Pagan, J. C.; Bosch, J.; Arroyo, V.; Gines, P.; Caballeria, J.; Bataller, R. Hepatic expression of CXC chemokines predicts portal hypertension and survival in patients with alcoholic hepatitis. Gastroenterology, 2009, 136 (5), 1639-1650.
50. Huang, Y. S.; Chan, C. Y.; Wu, J. C.; Pai, C. H.; Chao, Y.; Lee, S. D. Serum levels of interleukin-8 in alcoholic liver disease: relationship with disease stage, biochemical parameters and survival. J. Hepatol., 1996, 24 (4), 377-384.
51. Ciecko-Michalska, I.; Szczepanek, M.; Cibor, D.; Owczarek, D.; Skulina, D.; Szczepanski, W.; Michalski, M. Serum cytokine concentration as prognostic factor in patients with alcoholic liver disease. Przegl. Lek., 2006, 63 (5), 249-252.
52. Zimmermann, H. W.; Seidler, S.; Gassler, N.; Nattermann, J.; Luedde, T.; Trautwein, C.; Tacke, F. Interleukin-8 is activated in patients with chronic liver diseases and associated with hepatic macrophage accumulation in human liver fibrosis. PLoS One, 2011, 6 (6), e21381.
53. Polyak, S. J.; Khabar, K. S.; Rezeiq, M.; Gretch, D. R. Elevated levels of interleukin-8 in serum are associated with hepatitis C virus infection and resistance to interferon therapy. J. Virol., 2001, 75 (13), 6209-6211.
54. El Sayed, Z. M.; Mansour, F. A.; Ghal, M. F.; Abou-Zahra, S. B. Evaluation of interleukin-8 in hepatitis C virus infection: relation to combined peg-interferon ribavirin response and genotype 4. Immunol. Invest., 2011, 40 (1), 29-38.
55. Saito, J. M.; Bostick, M. K.; Campe, C. B.; Xu, J.; Maher, J. J. Infiltrating neutrophils in bile duct-ligated livers do not promote hepatic fibrosis. Hepatol. Res., 2003, 25 (2), 180-191.
56. Isse, K.; Harada, K.; Nakanuma, Y. IL-8 expression by biliary epithelial cells is associated with neutrophilic infiltration and reactive bile ductules. Liver Int., 2007, 27 (5), 672-680.
57. Harty, M. W.; Huddleston, H. M.; Papa, E. F.; Puthawala, T.; Tracy, A. P.; Ramm, G. A.; Gehring, S.; Gregory, S. H.; Tracy, T. F., Jr. Repair after cholestatic liver injury correlates with neutrophil infiltration and matrix metalloproteinase 8 activity. Surgery, 2005, 138 (2), 313-320.
58. Harty, M. W.; Papa, E. F.; Huddleston, H. M.; Young, E.; Nazareth, S.; Riley, C. A.; Ramm, G. A.; Gregory, S. H.; Tracy, T. F., Jr. Hepatic macrophages promote the neutrophil-dependent resolution of fibrosis in repairing cholestatic rat livers. Surgery, 2008, 143 (5), 667-678.
59. Harty, M. W.; Muratore, C. S.; Papa, E. F.; Gart, M. S.; Ramm, G. A.; Gregory, S. H.; Tracy, T. F., Jr. Neutrophil depletion blocks early collagen degradation in repairing cholestatic rat livers. Am. J. Pathol., 2010, 176 (3), 1271-1281.
60. Okayama, Y.; Kawakami, T. Development, migration, and survival of mast cells. Immunol. Res., 2006, 34 (2), 97-115.
61. Kitamura, Y.; Fujita, J. Regulation of mast cell differentiation. Bioessays, 1989, 10 (6), 193-196.
62. Hatanaka, K.; Kitamura, Y.; Nishimune, Y. Local development of mast cells from bone marrow-derived precursors in the skin of mice. Blood, 1979, 53 (1), 142-147.
63. Franceschini, B.; Ceva-Grimaldi, G.; Russo, C.; Dioguardi, N.; Grizzi, F. The complex functions of mast cells in chronic human liver diseases. Dig. Dis. Sci., 2006, 51 (12), 2248-2256.
64. Juremalm, M.; Nilsson, G. Chemokine receptor expression by mast cells. Chem. Immunol. Allergy, 2005, 87, 130-144.
65. Franceschini, B.; Russo, C.; Dioguardi, N.; Grizzi, F. Increased liver mast cell recruitment in patients with chronic C virus-related hepatitis and histologically documented steatosis. J. Viral. Hepat., 2007, 14 (8), 549-555.
66. Yamashiro, M.; Kouda, W.; Kono, N.; Tsuneyama, K.; Matsui, O.; Nakanuma, Y. Distribution of intrahepatic mast cells in various hepatobiliary disorders. An immunohistochemical study. Virchows. Arch., 1998, 433 (5), 471-479.
67. Farrell, D. J.; Hines, J. E.; Walls, A. F.; Kelly, P. J.; Bennett, M. K.; Burt, A. D. Intrahepatic mast cells in chronic liver diseases. Hepatology, 1995, 22 (4 Pt 1), 1175-1181.
68. Matsunaga, Y.; Kawasaki, H.; Terada, T. Stromal mast cells and nerve fibers in various chronic liver diseases: relevance to hepatic fibrosis. Am. J. Gastroenterol., 1999, 94 (7), 1923-1932.
69. Armbrust, T.; Batusic, D.; Ringe, B.; Ramadori, G. Mast cells distribution in human liver disease and experimental rat liver fibrosis. Indications for mast cell participation in development of liver fibrosis. J. Hepatol., 1997, 26 (5), 1042-1054.
70. Peng, R. Y.; Wang, D. W.; Xu, Z. H.; Gao, Y. B.; Yang, R. B.; Liu, P.; Wang, Z. P.; Li, Y. P. The changes and significance of mast cells in irradiated rat liver. J. Environ. Pathol. Toxicol. Oncol., 1994, 13 (2), 111-116.
71. Xu, X.; Ruan, Y. B.; Wu, Z. B. Study on the role of mast cells in the development of liver fibrosis during diethylnitrosamine (DEN) -induced hepatocarcinogenesis in rats. J. Tongji. Med. Univ., 1994, 14 (4), 193-199.
72. Akiyoshi, H.; Terada, T. Mast cell, myofibroblast and nerve terminal complexes in carbon tetrachloride-induced cirrhotic rat livers. J. Hepatol., 1998, 29 (1), 112-119.
73. Rioux, K. P.; Sharkey, K. A.; Wallace, J. L.; Swain, M. G. Hepatic mucosal mast cell hyperplasia in rats with secondary biliary cirrhosis. Hepatology, 1996, 23 (4), 888-895.
74. Yoshida, M.; Nishikawa, Y.; Yamamoto, Y.; Doi, Y.; Tokairin, T.; Yoshioka, T.; Omori, Y.; Watanabe, A.; Takahashi, N.; Miura, I.; Sawada, K.; Enomoto, K. Mast cell leukemia with rapidly progressing portal hypertension. Pathol. Int., 2009, 59 (11), 817-822.
75. Kyriakou, D.; Kouroumalis, E.; Konsolas, J.; Oekonomaki, H.; Tzardi, M.; Kanavaros, P.; Manoussos, O.; Eliopoulos, G. D. Systemic mastocytosis: a rare cause of noncirrhotic portal hypertension simulating autoimmune cholangitis--report of four cases. Am. J. Gastroenterol., 1998, 93 (1), 106-108.
76. Inoue, K.; Yoshioka, K.; Kasamatsu, Y.; Kawahito, Y.; Yokoo, S.; Kobayashi, Y.; Kondo, M. Bone marrow mast cell disease associated with Felty's syndrome and liver cirrhosis. Am. J. Hematol., 1998, 59 (2), 179.
77. Mican, J. M.; Di Bisceglie, A. M.; Fong, T. L.; Travis, W. D.; Kleiner, D. E.; Baker, B.; Metcalfe, D. D. Hepatic involvement in mastocytosis: clinicopathologic correlations in 41 cases. Hepatology, 1995, 22 (4 Pt 1), 1163-1170.
78. Cairns, J. A.; Walls, A. F. Mast cell tryptase stimulates the synthesis of type I collagen in human lung fibroblasts. J. Clin. Invest., 1997, 99 (6), 1313-1321.
79. Gruber, B. L.; Kew, R. R.; Jelaska, A.; Marchese, M. J.; Garlick, J.; Ren, S.; Schwartz, L. B.; Korn, J. H. Human mast cells activate fibroblasts: tryptase is a fibrogenic factor stimulating collagen messenger ribonucleic acid synthesis and fibroblast chemotaxis. J. Immunol., 1997, 158 (5), 2310-2317.
80. Tsuneyama, K.; Kono, N.; Yamashiro, M.; Kouda, W.; Sabit, A.; Sasaki, M.; Nakanuma, Y. Aberrant expression of stem cell factor on biliary epithelial cells and peribiliary infiltration of c-kit-expressing mast cells in hepatolithiasis and primary sclerosing cholangitis: a possible contribution to bile duct fibrosis. J. Pathol., 1999, 189 (4), 609-614.
81. Satomura, K.; Yin, M.; Shimizu, S.; Kato, Y.; Nagano, T.; Komeichi, H.; Ohsuga, M.; Katsuta, Y.; Aramaki, T.; Omoto, Y. Increased chymase in livers with autoimmune disease: colocalization with fibrosis. J. Nihon. Med. Sch., 2003, 70 (6), 490-495.
82. Ozaki, S.; Sato, Y.; Yasoshima, M.; Harada, K.; Nakanuma, Y. Diffuse expression of heparan sulfate proteoglycan and connective tissue growth factor in fibrous septa with many mast cells relate to unresolving hepatic fibrosis of congenital hepatic fibrosis. Liver Int., 2005, 25 (4), 817-828.
83. Okazaki, T.; Hirota, S.; Xu, Z. D.; Maeyama, K.; Nakama, A.; Kawano, S.; Hori, M.; Kitamura, Y. Increase of mast cells in the liver and lung may be associated with but not a cause of fibrosis: demonstration using mast cell-deficient Ws/Ws rats. Lab. Invest., 1998, 78 (11), 1431-148.
84. Sugihara, A.; Tsujimura, T.; Fujita, Y.; Nakata, Y.; Terada, N. Evaluation of role of mast cells in the development of liver fibrosis using mast cell-deficient rats and mice. J. Hepatol., 1999, 30 (5), 859-867.
85. Shamri, R.; Xenakis, J. J.; Spencer, L. A. Eosinophils in innate immunity: an evolving story. Cell Tissue Res., 2011, 343 (1), 57-83.
86. Kariyawasam, H. H.; Robinson, D. S. The role of eosinophils in airway tissue remodelling in asthma. Curr. Opin. Immunol., 2007, 19 (6), 681-686.
87. Rothenberg, M. E.; MacLean, J. A.; Pearlman, E.; Luster, A. D.; Leder, P. Targeted disruption of the chemokine eotaxin partially reduces antigen-induced tissue eosinophilia. J. Exp. Med., 1997, 185 (4), 785-790.
88. Humbles, A. A.; Lu, B.; Friend, D. S.; Okinaga, S.; Lora, J.; Al-Garawi, A.; Martin, T. R.; Gerard, N. P.; Gerard, C. The murine CCR3 receptor regulates both the role of eosinophils and mast cells in allergen-induced airway inflammation and hyperresponsiveness. Proc. Natl. Acad. Sci. USA., 2002, 99 (3), 1479-1484.
89. Swartz, J. M.; Dyer, K. D.; Cheever, A. W.; Ramalingam, T.; Pesnicak, L.; Domachowske, J. B.; Lee, J. J.; Lee, N. A.; Foster, P. S.; Wynn, T. A.; Rosenberg, H. F. Schistosoma mansoni infection in eosinophil lineage-ablated mice. Blood, 2006, 108 (7), 2420-2427.
90. Behm, C. A.; Ovington, K. S. The role of eosinophils in parasitic helminth infections: insights from genetically modified mice. Parasitol. Today, 2000, 16 (5), 202-209.
91. Meeusen, E. N.; Balic, A. Do eosinophils have a role in the killing of helminth parasites? Parasitol. Today, 2000, 16 (3), 95-101.
92. Burke, M. L.; McManus, D. P.; Ramm, G. A.; Duke, M.; Li, Y.; Jones, M. K.; Gobert, G. N. Temporal expression of chemokines dictates the hepatic inflammatory infiltrate in a murine model of schistosomiasis. PLoS Negl. Trop. Dis., 2010, 4 (2), e598.
93. Tian, L.; Li, W.; Wang, J.; Zhang, Y.; Zheng, Y.; Qi, H.; Guo, X.; Ma, D.; Shen, H.; Wang, Y. The CKLF1-C19 peptide attenuates allergic lung inflammation by inhibiting CCR3- and CCR4-mediated chemotaxis in a mouse model of asthma. Allergy, 2011, 66 (2), 287-297.
94. Fryer, A. D.; Stein, L. H.; Nie, Z.; Curtis, D. E.; Evans, C. M.; Hodgson, S. T.; Jose, P. J.; Belmonte, K. E.; Fitch, E.; Jacoby, D. B. Neuronal eotaxin and the effects of CCR3 antagonist on airway hyperreactivity and M2 receptor dysfunction. J. Clin. Invest., 2006, 116 (1), 228-236.
95. Erin, E. M.; Williams, T. J.; Barnes, P. J.; Hansel, T. T. Eotaxin receptor (CCR3) antagonism in asthma and allergic disease. Curr. Drug Targets Inflamm. Allergy 2002, 1 (2), 201-214.
96. Pham, B. N.; Bemuau, J.; Durand, F.; Sauvanet, A.; Degott, C.; Prin, L.; Janin, A. Eotaxin expression and eosinophil infiltrate in the liver of patients with drug-induced liver disease. J. Hepatol., 2001, 34 (4), 537-547.
97. Tacke, F.; Trautwein, C.; Yagmur, E.; Hellerbrand, C.; Wiest, R.; Brenner, D. A.; Schnabl, B. Up-regulated eotaxin plasma levels in chronic liver disease patients indicate hepatic inflammation, advanced fibrosis and adverse clinical course. J. Gastroenterol. Hepatol., 2007, 22 (8), 1256-1264.
98. Terasaki, S.; Nakanuma, Y.; Yamazaki, M.; Unoura, M. Eosinophilic infiltration of the liver in primary biliary cirrhosis: a morphological study. Hepatology, 1993, 17 (2), 206-212.
99. Watanabe, H.; Ohira, H.; Kuroda, M.; Takagi, T.; Ishikawa, H.; Nishimaki, T.; Kasukawa, R.; Takahashi, K. Primary sclerosing cholangitis with marked eosinophilic infiltration in the liver. J. Gastroenterol., 1995, 30 (4), 524-528.
100. Nakamura, A.; Yamazaki, K.; Suzuki, K.; Sato, S. Increased portal tract infiltration of mast cells and eosinophils in primary biliary cirrhosis. Am. J. Gastroenterol., 1997, 92 (12), 2245-2249.
101. Tarantino, G.; Cabibi, D.; Camma, C.; Alessi, N.; Donatelli, M.; Petta, S.; Craxi, A.; Di Marco, V. Liver eosinophilic infiltrate is a significant finding in patients with chronic hepatitis C. J. Viral. Hepat., 2008, 15 (7), 523-530.
102. Tsuda, K.; Maeda, T.; Tominaga, A.; Watanabe, Y.; Miyazaki, E.; Enzan, H.; Akisawa, N.; Iwasaki, S.; Saibara, T.; Onishi, S. Eosinophil-induced liver injury: an experimental model using IL-5 transgenic mice. J. Hepatol., 2001, 34 (2), 270-277.
103. Gale, R. P.; Sparkes, R. S.; Golde, D. W. Bone marrow origin of hepatic macrophages (Kupffer cells) in humans. Science, 1978, 201 (4359), 937-8.
104. Klein, I.; Cornejo, J. C.; Polakos, N. K.; John, B.; Wuensch, S. A.; Topham, D. J.; Pierce, R. H.; Crispe, I. N. Kupffer cell heterogeneity: functional properties of bone marrow derived and sessile hepatic macrophages. Blood, 2007, 110 (12), 4077-4085.
105. Karlmark, K. R.; Weiskirchen, R.; Zimmermann, H. W.; Gassler, N.; Ginhoux, F.; Weber, C.; Merad, M.; Luedde, T.; Trautwein, C.; Tacke, F. Hepatic recruitment of the inflammatory Gr1+ monocyte subset upon liver injury promotes hepatic fibrosis. Hepatology, 2009, 50 (1), 261-274.
106. Jenkins, S. J.; Ruckerl, D.; Cook, P. C.; Jones, L. H.; Finkelman, F. D.; van Rooijen, N.; MacDonald, A. S.; Allen, J. E. Local macrophage proliferation, rather than recruitment from the blood, is a signature of TH2 inflammation. Science, 2011, 332 (6035), 1284-1288.
107. Knolle, P.; Schlaak, J.; Uhrig, A.; Kempf, P.; Meyer zum Buschenfelde, K. H.; Gerken, G. Human Kupffer cells secrete IL-10 in response to lipopolysaccharide (LPS) challenge. J. Hepatol., 1995, 22 (2), 226-229.
108. Knolle, P. A.; Uhrig, A.; Hegenbarth, S.; Loser, E.; Schmitt, E.; Gerken, G.; Lohse, A. W. IL-10 down-regulates T cell activation by antigen-presenting liver sinusoidal endothelial cells through decreased antigen uptake via the mannose receptor and lowered surface expression of accessory molecules. Clin. Exp. Immunol., 1998, 114 (3), 427-433.
109. Diesselhoff-den Dulk, M. M.; Crofton, R. W.; van Furth, R. Origin and kinetics of Kupffer cells during an acute inflammatory response. Immunology, 1979, 37 (1), 7-14.
110. Crofton, R. W.; Diesselhoff-den Dulk, M. M.; van Furth, R. The origin, kinetics, and characteristics of the Kupffer cells in the normal steady state. J. Exp. Med., 1978, 148 (1), 1-17.
111. Imamura, M.; Ogawa, T.; Sasaguri, Y.; Chayama, K.; Ueno, H. Suppression of macrophage infiltration inhibits activation of hepatic stellate cells and liver fibrogenesis in rats. Gastroenterology, 2005, 128 (1), 138-146.
112. Mitchell, C.; Couton, D.; Couty, J. P.; Anson, M.; Crain, A. M.; Bizet, V.; Renia, L.; Pol, S.; Mallet, V.; Gilgenkrantz, H. Dual role of CCR2 in the constitution and the resolution of liver fibrosis in mice. Am. J. Pathol., 2009, 174 (5), 1766-1775.
113. Zimmermann, H. W.; Seidler, S.; Nattermann, J.; Gassler, N.; Hellerbrand, C.; Zernecke, A.; Tischendorf, J. J.; Luedde, T.; Weiskirchen, R.; Trautwein, C.; Tacke, F. Functional contribution of elevated circulating and hepatic non-classical CD14CD16 monocytes to inflammation and human liver fibrosis. PLoS One, 2010, 5 (6), e11049.
114. Ide, M.; Yamate, J.; Machida, Y.; Nakanishi, M.; Kuwamura, M.; Kotani, T.; Sawamoto, O., Emergence of different macrophage populations in hepatic fibrosis following thioacetamide-induced acute hepatocyte injury in rats. J. Comp. Pathol., 2003, 128 (1), 41-51.
115. Ide, M.; Kuwamura, M.; Kotani, T.; Sawamoto, O.; Yamate, J. Effects of gadolinium chloride (GdCl(3)) on the appearance of macrophage populations and fibrogenesis in thioacetamide-induced rat hepatic lesions. J. Comp. Pathol., 2005, 133 (2-3), 92-102.
116. Rivera, C. A.; Bradford, B. U.; Hunt, K. J.; Adachi, Y.; Schrum, L. W.; Koop, D. R.; Burchardt, E. R.; Rippe, R. A.; Thurman, R. G. Attenuation of CCl(4)-induced hepatic fibrosis by GdCl(3) treatment or dietary glycine. Am. J. Physiol. Gastrointest. Liver Physiol., 2001, 281 (1), G200-207.
117. Duffield, J. S.; Forbes, S. J.; Constandinou, C. M.; Clay, S.; Partolina, M.; Vuthoori, S.; Wu, S.; Lang, R.; Iredale, J. P. Selective depletion of macrophages reveals distinct, opposing roles during liver injury and repair. J. Clin. Invest., 2005, 115 (1), 56-65.
118. Leicester, K. L.; Olynyk, J. K.; Brunt, E. M.; Britton, R. S.; Bacon, B. R. Differential findings for CD14-positive hepatic monocytes/macrophages in primary biliary cirrhosis, chronic hepatitis C and nonalcoholic steatohepatitis. Liver Int., 2006, 26 (5), 559-565.
119. McGuinness, P. H.; Painter, D.; Davies, S.; McCaughan, G. W. Increases in intrahepatic CD68 positive cells, MAC387 positive cells, and proinflammatory cytokines (particularly interleukin 18) in chronic hepatitis C infection. Gut, 2000, 46 (2), 260-269.
120. Kitani, A.; Fuss, I.; Nakamura, K.; Kumaki, F.; Usui, T.; Strober, W. Transforming growth factor (TGF)-beta1-producing regulatory T cells induce Smad-mediated interleukin 10 secretion that facilitates coordinated immunoregulatory activity and amelioration of TGF-beta1-mediated fibrosis. J. Exp. Med., 2003, 198 (8), 1179-88.
121. Seki, E.; De Minicis, S.; Osterreicher, C. H.; Kluwe, J.; Osawa, Y.; Brenner, D. A.; Schwabe, R. F. TLR4 enhances TGF-beta signaling and hepatic fibrosis. Nat. Med., 2007, 13 (11), 1324-1332.
122. Fadok, V. A.; Bratton, D. L.; Konowal, A.; Freed, P. W.; Westcott, J. Y.; Henson, P. M. Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine/paracrine mechanisms involving TGF-beta, PGE2, and PAF. J. Clin. Invest., 1998, 101 (4), 890-898.
123. Hotchkiss, R. S.; Strasser, A.; McDunn, J. E.; Swanson, P. E. Cell death. N. Engl. J. Med., 2009, 361 (16), 1570-1583.
124. Rock, K. L.; Kono, H. The inflammatory response to cell death. Annu. Rev. Pathol., 2008, 3, 99-126.
125. Wynn, T. A. Common and unique mechanisms regulate fibrosis in various fibroproliferative diseases. J. Clin. Invest., 2007, 117 (3), 524-529.
126. Bonner, J. C. Regulation of PDGF and its receptors in fibrotic diseases. Cytokine Growth Factor Rev., 2004, 15 (4), 255-273.
127. Friedman, S. L.; Arthur, M. J. Activation of cultured rat hepatic lipocytes by Kupffer cell conditioned medium. Direct enhancement of matrix synthesis and stimulation of cell proliferation via induction of platelet-derived growth factor receptors. J. Clin. Invest., 1989, 84 (6), 1780-1785.
128. Tiggelman, A. M.; Boers, W.; Linthorst, C.; Sala, M.; Chamuleau, R. A. Collagen synthesis by human liver (myo)fibroblasts in culture: evidence for a regulatory role of IL-1 beta, IL-4, TGF beta and IFN gamma. J. Hepatol., 1995, 23 (3), 307-317.
129. Mancini, R.; Benedetti, A.; Jezequel, A. M. An interleukin-1 receptor antagonist decreases fibrosis induced by dimethylnitrosamine in rat liver. Virchows Arch., 1994, 424 (1), 25-31.
130. Wynes, M. W.; Riches, D. W. Induction of macrophage insulin-like growth factor-I expression by the Th2 cytokines IL-4 and IL-13. J. Immunol., 2003, 171 (7), 3550-3559.
131. Povero, D.; Busletta, C.; Novo, E.; di Bonzo, L. V.; Cannito, S.; Paternostro, C.; Parola, M. Liver fibrosis: a dynamic and potentially reversible process. Histol. Histopathol., 2010, 25 (8), 1075-1091.
132. Wynn, T. A.; Barron, L. Macrophages: master regulators of inflammation and fibrosis. Semin. Liver Dis., 2010, 30 (3), 245-257.
133. Gordon, S.; Martinez, F. O. Alternative activation of macrophages: mechanism and functions. Immunity, 2010, 32 (5), 593-604.
134. Wynn, T. A. Fibrotic disease and the T(H)1/T(H)2 paradigm. Nat. Rev. Immunol., 2004, 4 (8), 583-594.
135. Liu, T.; Hu, B.; Choi, Y. Y.; Chung, M.; Ullenbruch, M.; Yu, H.; Lowe, J. B.; Phan, S. H. Notch1 signaling in FIZZ1 induction of myofibroblast differentiation. Am. J. Pathol., 2009, 174 (5), 1745-1755.
136. Gratchev, A.; Guillot, P.; Hakiy, N.; Politz, O.; Orfanos, C. E.; Schledzewski, K.; Goerdt, S. Alternatively activated macrophages differentially express fibronectin and its splice variants and the extracellular matrix protein betaIG-H3. Scand. J. Immunol., 2001, 53 (4), 386-392.
137. Shearer, J. D.; Richards, J. R.; Mills, C. D.; Caldwell, M. D. Differential regulation of macrophage arginine metabolism: a proposed role in wound healing. Am. J. Physiol., 1997, 272 (2 Pt 1), E181-190.
138. Endo, M.; Oyadomari, S.; Terasaki, Y.; Takeya, M.; Suga, M.; Mori, M.; Gotoh, T. Induction of arginase I and II in bleomycin-induced fibrosis of mouse lung. Am. J. Physiol. Lung Cell Mol. Physiol., 2003, 285 (2), L313-321.
139. Pesce, J. T.; Ramalingam, T. R.; Mentink-Kane, M. M.; Wilson, M. S.; El Kasmi, K. C.; Smith, A. M.; Thompson, R. W.; Cheever, A. W.; Murray, P. J.; Wynn, T. A. Arginase-1-expressing macrophages suppress Th2 cytokine-driven inflammation and fibrosis. PLoS Pathog., 2009, 5 (4), e1000371.
140. Hesse, M.; Cheever, A. W.; Jankovic, D.; Wynn, T. A. NOS-2 mediates the protective anti-inflammatory and antifibrotic effects of the Th1-inducing adjuvant, IL-12, in a Th2 model of granulomatous disease. Am. J. Pathol., 2000, 157 (3), 945-955.
141. Hesse, M.; Modolell, M.; La Flamme, A. C.; Schito, M.; Fuentes, J. M.; Cheever, A. W.; Pearce, E. J.; Wynn, T. A. Differential regulation of nitric oxide synthase-2 and arginase-1 by type 1/type 2 cytokines in vivo: granulomatous pathology is shaped by the pattern of L-arginine metabolism. J. Immunol., 2001, 167 (11), 6533-6544.
142. Herbert, D. R.; Holscher, C.; Mohrs, M.; Arendse, B.; Schwegmann, A.; Radwanska, M.; Leeto, M.; Kirsch, R.; Hall, P.; Mossmann, H.; Claussen, B.; Forster, I.; Brombacher, F. Alternative macrophage activation is essential for survival during schistosomiasis and downmodulates T helper 1 responses and immunopathology. Immunity, 2004, 20 (5), 623-635.
143. Tacke, F.; Kurts, C. Infiltrating monocytes vs resident Kupffer cells - do alternatively activated macrophages need to be targeted alternatively? Hepatology, 2011, in press.
144. Geissmann, F.; Manz, M. G.; Jung, S.; Sieweke, M. H.; Merad, M.; Ley, K. Development of monocytes, macrophages, and dendritic cells. Science, 2010, 327 (5966), 656-661.
145. Auffray, C.; Sieweke, M. H.; Geissmann, F. Blood monocytes: development, heterogeneity, and relationship with dendritic cells. Ann. Rev. Immunol., 2009, 27, 669-692.
146. Tacke, F.; Randolph, G. J. Migratory fate and differentiation of blood monocyte subsets. Immunobiology, 2006, 211 (6-8), 609-618.
147. Zawada, A. M.; Rogacev, K. S.; Rotter, B.; Winter, P.; Marell, R. R.; Fliser, D.; Heine, G. H. SuperSAGE evidence for CD14++CD16+ monocytes as a third monocyte subset. Blood, 2011, 118 (12), e50-61.
148. Wong, K. L.; Tai, J. J.; Wong, W. C.; Han, H.; Sem, X.; Yeap, W. H.; Kourilsky, P.; Wong, S. C. Gene expression profiling reveals the defining features of the classical, intermediate, and nonclassical human monocyte subsets. Blood, 2011, 118 (5), e16-31.
149. Ziegler-Heitbrock, L.; Ancuta, P.; Crowe, S.; Dalod, M.; Grau, V.; Hart, D. N.; Leenen, P. J.; Liu, Y. J.; MacPherson, G.; Randolph, G. J.; Scherberich, J.; Schmitz, J.; Shortman, K.; Sozzani, S.; Strobl, H.; Zembala, M.; Austyn, J. M.; Lutz, M. B. Nomenclature of monocytes and dendritic cells in blood. Blood, 2010, 116 (16), e74-80.
150. Gordon, S.; Taylor, P. R. Monocyte and macrophage heterogeneity. Nat. Rev. Immunol., 2005, 5 (12), 953-964.
151. Geissmann, F.; Jung, S.; Littman, D. R. Blood monocytes consist of two principal subsets with distinct migratory properties. Immunity, 2003, 19 (1), 71-82.
152. Ziegler-Heitbrock, L. The CD14+ CD16+ blood monocytes: their role in infection and inflammation. J. Leukoc. Biol., 2007, 81 (3), 584-592.
153. Serbina, N. V.; Pamer, E. G. Monocyte emigration from bone marrow during bacterial infection requires signals mediated by chemokine receptor CCR2. Nat. Immunol., 2006, 7 (3), 311-317.
154. Swirski, F. K.; Robbins, C. S. The multiple roles of monocyte subsets in steady state and inflammation. Cell Mol. Life Sci., 2010, 67 (16), 2685-2693.
155. Tacke, F.; Alvarez, D.; Kaplan, T. J.; Jakubzick, C.; Spanbroek, R.; Llodra, J.; Garin, A.; Liu, J.; Mack, M.; van Rooijen, N.; Lira, S. A.; Habenicht, A. J.; Randolph, G. J. Monocyte subsets differentially employ CCR2, CCR5, and CX3CR1 to accumulate within atherosclerotic plaques. J. Clin. Invest., 2007, 117 (1), 185-194.
156. Robays, L. J.; Maes, T.; Lebecque, S.; Lira, S. A.; Kuziel, W. A.; Brusselle, G. G.; Joos, G. F.; Vermaelen, K. V. Chemokine receptor CCR2 but not CCR5 or CCR6 mediates the increase in pulmonary dendritic cells during allergic airway inflammation. J. Immunol., 2007, 178 (8), 5305-5311.
157. Ingersoll, M. A.; Spanbroek, R.; Lottaz, C.; Gautier, E. L.; Frankenberger, M.; Hoffmann, R.; Lang, R.; Haniffa, M.; Collin, M.; Tacke, F.; Habenicht, A. J.; Ziegler-Heitbrock, L.; Randolph, G. J. Comparison of gene expression profiles between human and mouse monocyte subsets. Blood, 2010, 115 (3), e10-9.
158. Randolph, G. J.; Sanchez-Schmitz, G.; Liebman, R. M.; Schakel, K. The CD16(+) (FcgammaRIII(+)) subset of human monocytes preferentially becomes migratory dendritic cells in a model tissue setting. J. Exp. Med., 2002, 196 (4), 517-527.
159. Auffray, C.; Fogg, D.; Garfa, M.; Elain, G.; Join-Lambert, O.; Kayal, S.; Sarnacki, S.; Cumano, A.; Lauvau, G.; Geissmann, F. Monitoring of blood vessels and tissues by a population of monocytes with patrolling behavior. Science, 2007, 317 (5838), 666-670.
160. Belge, K. U.; Dayyani, F.; Horelt, A.; Siedlar, M.; Frankenberger, M.; Frankenberger, B.; Espevik, T.; Ziegler-Heitbrock, L. The proinflammatory CD14+CD16+DR++ monocytes are a major source of TNF. J. Immunol., 2002, 168 (7), 3536-3542.
161. Shi, C.; Velazquez, P.; Hohl, T. M.; Leiner, I.; Dustin, M. L.; Pamer, E. G. Monocyte trafficking to hepatic sites of bacterial infection is chemokine independent and directed by focal intercellular adhesion molecule-1 expression. J. Immunol., 2010, 184 (11), 6266-6274.
162. Zamara, E.; Galastri, S.; Aleffi, S.; Petrai, I.; Aragno, M.; Mastrocola, R.; Novo, E.; Bertolani, C.; Milani, S.; Vizzutti, F.; Vercelli, A.; Pinzani, M.; Laffi, G.; LaVilla, G.; Parola, M.; Marra, F. Prevention of severe toxic liver injury and oxidative stress in MCP-1-deficient mice. J. Hepatol., 2007, 46 (2), 230-238.
163. Czaja, M. J.; Geerts, A.; Xu, J.; Schmiedeberg, P.; Ju, Y. Monocyte chemoattractant protein 1 (MCP-1) expression occurs in toxic rat liver injury and human liver disease. J. Leukoc. Biol., 1994, 55 (1), 120-126.
164. Marra, F.; DeFranco, R.; Grappone, C.; Milani, S.; Pastacaldi, S.; Pinzani, M.; Romanelli, R. G.; Laffi, G.; Gentilini, P. Increased expression of monocyte chemotactic protein-1 during active hepatic fibrogenesis: correlation with monocyte infiltration. Am. J. Pathol., 1998, 152 (2), 423-430.
165. Karlmark, K. R.; Wasmuth, H. E.; Trautwein, C.; Tacke, F. Chemokine-directed immune cell infiltration in acute and chronic liver disease. Expert. Rev. Gastroenterol. Hepatol., 2008, 2 (2), 233-242.
166. Kirovski, G.; Dorn, C.; Huber, H.; Moleda, L.; Niessen, C.; Wobser, H.; Schacherer, D.; Buechler, C.; Wiest, R.; Hellerbrand, C. Elevated systemic monocyte chemoattractrant protein-1 in hepatic steatosis without significant hepatic inflammation. Exp. Mol. Pathol., 2011 [Epub ahead of print].
167. Tsuruta, S.; Nakamuta, M.; Enjoji, M.; Kotoh, K.; Hiasa, K.; Egashira, K.; Nawata, H. Anti-monocyte chemoattractant protein-1 gene therapy prevents dimethylnitrosamine-induced hepatic fibrosis in rats. Int. J. Mol. Med., 2004, 14 (5), 837-842.
168. Seki, E.; de Minicis, S.; Inokuchi, S.; Taura, K.; Miyai, K.; van Rooijen, N.; Schwabe, R. F.; Brenner, D. A. CCR2 promotes hepatic fibrosis in mice. Hepatology, 2009, 50 (1), 185-197.
169. Sakai, N.; Wada, T.; Furuichi, K.; Shimizu, K.; Kokubo, S.; Hara, A.; Yamahana, J.; Okumura, T.; Matsushima, K.; Yokoyama, H.; Kaneko, S. MCP-1/CCR2-dependent loop for fibrogenesis in human peripheral CD14-positive monocytes. J. Leukoc. Biol., 2006, 79 (3), 555-563.
170. Obstfeld, A. E.; Sugaru, E.; Thearle, M.; Francisco, A. M.; Gayet, C.; Ginsberg, H. N.; Ables, E. V.; Ferrante, A. W. Jr. C-C chemokine receptor 2 (CCR2) regulates the hepatic recruitment of myeloid cells that promote obesity-induced hepatic steatosis. Diabetes, 2010, 59 (4), 916-925.
171. Kanda, H.; Tateya, S.; Tamori, Y.; Kotani, K.; Hiasa, K.; Kitazawa, R.; Kitazawa, S.; Miyachi, H.; Maeda, S.; Egashira, K.; Kasuga, M. MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity. J. Clin. Invest., 2006, 116 (6), 1494-1505.
172. Rull, A.; Rodriguez, F.; Aragones, G.; Marsillach, J.; Beltran, R.; Alonso-Villaverde, C.; Camps, J.; Joven, J. Hepatic monocyte chemoattractant protein-1 is upregulated by dietary cholesterol and contributes to liver steatosis. Cytokine, 2009, 48 (3), 273-279.
173. Yang, S. J.; IglayReger, H. B.; Kadouh, H. C.; Bodary, P. F. Inhibition of the chemokine (C-C motif) ligand 2/chemokine (C-C motif) receptor 2 pathway attenuates hyperglycaemia and inflammation in a mouse model of hepatic steatosis and lipoatrophy. Diabetologia, 2009, 52 (5), 972-981.
174. Tamura, Y.; Sugimoto, M.; Murayama, T.; Ueda, Y.; Kanamori, H.; Ono, K.; Ariyasu, H.; Akamizu, T.; Kita, T.; Yokode, M.; Arai, H. Inhibition of CCR2 ameliorates insulin resistance and hepatic steatosis in db/db mice. Arterioscler, Thromb. Vasc. Biol., 2008, 28 (12), 2195-2201.
175. Baeck, C.; Wehr, A.; Karlmark, K. R.; Heymann, F.; Vucur, M.; Gassler, N.; Huss, S.; Klussmann, S.; Eulberg, D.; Luedde, T.; Trautwein, C.; Tacke, F. Pharmacological inhibition of the chemokine CCL2 (MCP-1) diminishes liver macrophage infiltration and steatohepatitis in chronic hepatic injury. Gut, 2011 [Epub ahead of print].
176. Tsuneyama, K.; Harada, K.; Yasoshima, M.; Hiramatsu, K.; Mackay, C. R.; Mackay, I. R.; Gershwin, M. E.; Nakanuma, Y. Monocyte chemotactic protein-1, -2, and -3 are distinctively expressed in portal tracts and granulomata in primary biliary cirrhosis: implications for pathogenesis. J. Pathol., 2001, 193 (1), 102-109.
177. Jia, T.; Serbina, N. V.; Brandl, K.; Zhong, M. X.; Leiner, I. M.; Charo, I. F.; Pamer, E. G. Additive roles for MCP-1 and MCP-3 in CCR2-mediated recruitment of inflammatory monocytes during Listeria monocytogenes infection. J. Immunol., 2008, 180 (10), 6846-6853.
178. Hokeness, K. L.; Kuziel, W. A.; Biron, C. A.; Salazar-Mather, T. P. Monocyte chemoattractant protein-1 and CCR2 interactions are required for IFN-alpha/beta-induced inflammatory responses and antiviral defense in liver. J. Immunol., 2005, 174 (3), 1549-1556.
179. Weber, C.; Weber, K. S.; Klier, C.; Gu, S.; Wank, R.; Horuk, R.; Nelson, P. J. Specialized roles of the chemokine receptors CCR1 and CCR5 in the recruitment of monocytes and T(H)1-like/CD45RO(+) T cells. Blood, 2001, 97 (4), 1144-6.
180. Seki, E.; De Minicis, S.; Gwak, G. Y.; Kluwe, J.; Inokuchi, S.; Bursill, C. A.; Llovet, J. M.; Brenner, D. A.; Schwabe, R. F. CCR1 and CCR5 promote hepatic fibrosis in mice. J. Clin. Invest., 2009, 119 (7), 1858-1870.
181. Berres, M. L.; Koenen, R. R.; Rueland, A.; Zaldivar, M. M.; Heinrichs, D.; Sahin, H.; Schmitz, P.; Streetz, K. L.; Berg, T.; Gassler, N.; Weiskirchen, R.; Proudfoot, A.; Weber, C.; Trautwein, C.; Wasmuth, H. E. Antagonism of the chemokine Ccl5 ameliorates experimental liver fibrosis in mice. J. Clin. Invest., 2010, 120 (11), 4129-4140.
182. Heymann, F.; Hammerich, L.; Storch, D.; Bartneck, M.; Huss, S.; Rüsseler, V.; Gassler, N.; Lira, S. A.; Luedde, T.; Trautwein, C.; Tacke, F. Hepatic macrophage migration and differentiation critical for liver fibrosis is mediated by the chemokine receptor CCR8. Hepatology, 2012, in press.
183. Karlmark, K. R.; Zimmermann, H. W.; Roderburg, C.; Gassler, N.; Wasmuth, H. E.; Luedde, T.; Trautwein, C.; Tacke, F. The fractalkine receptor CX3CR1 protects against liver fibrosis by controlling differentiation and survival of infiltrating hepatic monocytes. Hepatology, 2010, 52 (5), 1769-1782.
184. Aoyama, T.; Inokuchi, S.; Brenner, D. A.; Seki, E. CX3CL1-CX3CR1 interaction prevents carbon tetrachloride-induced liver inflammation and fibrosis in mice. Hepatology, 2010, 52 (4), 1390-1400.
185. Aspinall, A. I.; Curbishley, S. M.; Lalor, P. F.; Weston, C. J.; Liaskou, E.; Adams, R. M.; Holt, A. P.; Adams, D. H. CX(3)CR1 and vascular adhesion protein-1-dependent recruitment of CD16(+) monocytes across human liver sinusoidal endothelium. Hepatology, 2010, 51 (6), 2030-2039.
186. Wasmuth, H. E.; Zaldivar, M. M.; Berres, M. L.; Werth, A.; Scholten, D.; Hillebrandt, S.; Tacke, F.; Schmitz, P.; Dahl, E.; Wiederholt, T.; Hellerbrand, C.; Berg, T.; Weiskirchen, R.; Trautwein, C.; Lammert, F., The fractalkine receptor CX3CR1 is involved in liver fibrosis due to chronic hepatitis C infection. J. Hepatol., 2008, 48 (2), 208-215.
187. Shimoda, S.; Harada, K.; Niiro, H.; Taketomi, A.; Maehara, Y.; Tsuneyama, K.; Kikuchi, K.; Nakanuma, Y.; Mackay, I. R.; Gershwin, M. E.; Akashi, K. CX3CL1 (fractalkine): a signpost for biliary inflammation in primary biliary cirrhosis. Hepatology, 2010, 51 (2), 567-575.
188. Fallowfield, J. A.; Mizuno, M.; Kendall, T. J.; Constandinou, C. M.; Benyon, R. C.; Duffield, J. S.; Iredale, J. P. Scar-associated macrophages are a major source of hepatic matrix metalloproteinase-13 and facilitate the resolution of murine hepatic fibrosis. J. Immunol., 2007, 178 (8), 5288-5295.
189. Thomas, J. A.; Pope, C.; Wojtacha, D.; Robson, A. J.; Gordon-Walker, T. T.; Hartland, S.; Ramachandran, P.; Van Deemter, M.; Hume, D. A.; Iredale, J. P.; Forbes, S. J. Macrophage therapy for murine liver fibrosis recruits host effector cells improving fibrosis, regeneration, and function. Hepatology, 2011, 53 (6), 2003-2015.
190. Gao, B.; Radaeva, S.; Park, O. Liver natural killer and natural killer T cells: immunobiology and emerging roles in liver diseases. J. Leukoc. Biol., 2009, 86 (3), 513-528.
191. Klugewitz, K.; Adams, D. H.; Emoto, M.; Eulenburg, K.; Hamann, A. The composition of intrahepatic lymphocytes: shaped by selective recruitment? Trends Immunol., 2004, 25 (11), 590-594.
192. Ajuebor, M. N.; Wondimu, Z.; Hogaboam, C. M.; Le, T.; Proudfoot, A. E.; Swain, M. G. CCR5 deficiency drives enhanced natural killer cell trafficking to and activation within the liver in murine T cell-mediated hepatitis. Am. J. Pathol., 2007, 170 (6), 1975-1988.
193. Cooper, M. A.; Fehniger, T. A.; Turner, S. C.; Chen, K. S.; Ghaheri, B. A.; Ghayur, T.; Carson, W. E.; Caligiuri, M. A. Human natural killer cells: a unique innate immunoregulatory role for the CD56(bright) subset. Blood, 2001, 97 (10), 3146-3151.
194. Notas, G.; Kisseleva, T.; Brenner, D. NK and NKT cells in liver injury and fibrosis. Clin. Immunol., 2009, 130 (1), 16-26.
195. Melhem, A.; Muhanna, N.; Bishara, A.; Alvarez, C. E.; Ilan, Y.; Bishara, T.; Horani, A.; Nassar, M.; Friedman, S. L.; Safadi, R. Anti-fibrotic activity of NK cells in experimental liver injury through killing of activated HSC. J. Hepatol., 2006, 45 (1), 60-71.
196. Radaeva, S.; Sun, R.; Jaruga, B.; Nguyen, V. T.; Tian, Z.; Gao, B. Natural killer cells ameliorate liver fibrosis by killing activated stellate cells in NKG2D-dependent and tumor necrosis factor-related apoptosis-inducing ligand-dependent manners. Gastroenterology, 2006, 130 (2), 435-452.
197. Radaeva, S.; Wang, L.; Radaev, S.; Jeong, W. I.; Park, O.; Gao, B. Retinoic acid signaling sensitizes hepatic stellate cells to NK cell killing via upregulation of NK cell activating ligand RAE1. Am. J. Physiol. Gastrointest. Liver Physiol., 2007, 293 (4), G809-816.
198. Muhanna, N.; Abu Tair, L.; Doron, S.; Amer, J.; Azzeh, M.; Mahamid, M.; Friedman, S.; Safadi, R. Amelioration of hepatic fibrosis by NK cell activation. Gut, 2011, 60 (1), 90-98.
199. Asseman, C.; Pancre, V.; Quatennens, B.; Auriault, C. Schistosoma mansoni-infected mice show augmented hepatic fibrosis and selective inhibition of liver cytokine production after treatment with anti-NK1.1 antibodies. Immunol. Lett., 1996, 54 (1), 11-20.
200. Robertson, M. J. Role of chemokines in the biology of natural killer cells. J. Leukoc. Biol., 2002, 71 (2), 173-183.
201. Moreno, C.; Gustot, T.; Nicaise, C.; Quertinmont, E.; Nagy, N.; Parmentier, M.; Le Moine, O.; Deviere, J.; Louis, H. CCR5 deficiency exacerbates T-cell-mediated hepatitis in mice. Hepatology, 2005, 42 (4), 854-862.
202. Khan, I. A.; Thomas, S. Y.; Moretto, M. M.; Lee, F. S.; Islam, S. A.; Combe, C.; Schwartzman, J. D.; Luster, A. D. CCR5 is essential for NK cell trafficking and host survival following Toxoplasma gondii infection. PLoS Pathog., 2006, 2 (6), e49.
203. Hintermann, E.; Bayer, M.; Pfeilschifter, J. M.; Luster, A. D.; Christen, U. CXCL10 promotes liver fibrosis by prevention of NK cell mediated hepatic stellate cell inactivation. J. Autoimmun., 2010, 35 (4), 424-435.
204. Margalit, M.; Abu Gazala, S.; Alper, R.; Elinav, E.; Klein, A.; Doviner, V.; Sherman, Y.; Thalenfeld, B.; Engelhardt, D.; Rabbani, E.; Ilan, Y. Glucocerebroside treatment ameliorates ConA hepatitis by inhibition of NKT lymphocytes. Am. J. Physiol. Gastrointest. Liver Physiol., 2005, 289 (5), G917-925.
205. Ajuebor, M. N.; Aspinall, A. I.; Zhou, F.; Le, T.; Yang, Y.; Urbanski, S. J.; Sidobre, S.; Kronenberg, M.; Hogaboam, C. M.; Swain, M. G. Lack of chemokine receptor CCR5 promotes murine fulminant liver failure by preventing the apoptosis of activated CD1d-restricted NKT cells. J. Immunol., 2005, 174 (12), 8027-8037.
206. Lisbonne, M.; L'Helgoualc'h, A.; Nauwelaers, G.; Turlin, B.; Lucas, C.; Herbelin, A.; Piquet-Pellorce, C.; Samson, M. Invariant natural killer T-cell-deficient mice display increased CCl -induced hepatitis associated with CXCL1 over-expression and neutrophil infiltration. Eur. J. Immunol., 2011, 41 (6), 1720-1732.
207. Park, O.; Jeong, W. I.; Wang, L.; Wang, H.; Lian, Z. X.; Gershwin, M. E.; Gao, B. Diverse roles of invariant natural killer T cells in liver injury and fibrosis induced by carbon tetrachloride. Hepatology, 2009, 49 (5), 1683-1694.
208. Syn, W. K.; Oo, Y. H.; Pereira, T. A.; Karaca, G. F.; Jung, Y.; Omenetti, A.; Witek, R. P.; Choi, S. S.; Guy, C. D.; Fearing, C. M.; Teaberry, V.; Pereira, F. E.; Adams, D. H.; Diehl, A. M. Accumulation of natural killer T cells in progressive nonalcoholic fatty liver disease. Hepatology, 2010, 51 (6), 1998-2007.
209. Safadi, R.; Zigmond, E.; Pappo, O.; Shalev, Z.; Ilan, Y., Amelioration of hepatic fibrosis via beta-glucosylceramide-mediated immune modulation is associated with altered CD8 and NKT lymphocyte distribution. Int. Immunol., 2007, 19 (8), 1021-1029.
210. Kakimi, K.; Guidotti, L. G.; Koezuka, Y.; Chisari, F. V. Natural killer T cell activation inhibits hepatitis B virus replication in vivo. J. Exp. Med., 2000, 192 (7), 921-930.
211. Jin, Z.; Sun, R.; Wei, H.; Gao, X.; Chen, Y.; Tian, Z. Accelerated liver fibrosis in hepatitis B virus transgenic mice: involvement of natural killer T cells. Hepatology, 2011, 53 (1), 219-229.
212. Ishikawa, S.; Ikejima, K.; Yamagata, H.; Aoyama, T.; Kon, K.; Arai, K.; Takeda, K.; Watanabe, S. CD1d-restricted natural killer T cells contribute to hepatic inflammation and fibrogenesis in mice. J. Hepatol., 2011, 54 (6), 1195-1204.
213. Geissmann, F.; Cameron, T. O.; Sidobre, S.; Manlongat, N.; Kronenberg, M.; Briskin, M. J.; Dustin, M. L.; Littman, D. R. Intravascular immune surveillance by CXCR6+ NKT cells patrolling liver sinusoids. PLoS Biol., 2005, 3 (4), e113.
214. Germanov, E.; Veinotte, L.; Cullen, R.; Chamberlain, E.; Butcher, E. C.; Johnston, B. Critical role for the chemokine receptor CXCR6 in homeostasis and activation of CD1d-restricted NKT cells. J. Immunol., 2008, 181 (1), 81-91.
215. Heydtmann, M.; Lalor, P. F.; Eksteen, J. A.; Hubscher, S. G.; Briskin, M.; Adams, D. H. CXC chemokine ligand 16 promotes integrin-mediated adhesion of liver-infiltrating lymphocytes to cholangiocytes and hepatocytes within the inflamed human liver. J. Immunol., 2005, 174 (2), 1055-1062.
216. Omenetti, A.; Syn, W. K.; Jung, Y.; Francis, H.; Porrello, A.; Witek, R. P.; Choi, S. S.; Yang, L.; Mayo, M. J.; Gershwin, M. E.; Alpini, G.; Diehl, A. M. Repair-related activation of hedgehog signaling promotes cholangiocyte chemokine production. Hepatology, 2009, 50 (2), 518-527.
217. Kita, H.; Naidenko, O. V.; Kronenberg, M.; Ansari, A. A.; Rogers, P.; He, X. S.; Koning, F.; Mikayama, T.; Van De Water, J.; Coppel, R. L.; Kaplan, M.; Gershwin, M. E. Quantitation and phenotypic analysis of natural killer T cells in primary biliary cirrhosis using a human CD1d tetramer. Gastroenterology, 2002, 123 (4), 1031-1043.
218. Wu, S. J.; Yang, Y. H.; Tsuneyama, K.; Leung, P. S.; Illarionov, P.; Gershwin, M. E.; Chuang, Y. H. Innate immunity and primary biliary cirrhosis: activated invariant natural killer T cells exacerbate murine autoimmune cholangitis and fibrosis. Hepatology, 2011, 53 (3), 915-925.
219. Johnston, B.; Kim, C. H.; Soler, D.; Emoto, M.; Butcher, E. C. Differential chemokine responses and homing patterns of murine TCR alpha beta NKT cell subsets. J. Immunol., 2003, 171 (6), 2960-2969.
220. Tacke, F.; Zimmermann, H. W.; Berres, M. L.; Trautwein, C.; Wasmuth, H. E. Serum chemokine receptor CXCR3 ligands are associated with progression, organ dysfunction and complications of chronic liver diseases. Liver Int., 2011, 31 (6), 840-849.
221. Dammacco, F.; Sansonno, D.; Piccoli, C.; Racanelli, V.; D'Amore, F. P.; Lauletta, G. The lymphoid system in hepatitis C virus infection: autoimmunity, mixed cryoglobulinemia, and Overt B-cell malignancy. Semin. Liver Dis., 2000, 20 (2), 143-157.
222. Novobrantseva, T. I.; Majeau, G. R.; Amatucci, A.; Kogan, S.; Brenner, I.; Casola, S.; Shlomchik, M. J.; Koteliansky, V.; Hochman, P. S.; Ibraghimov, A. Attenuated liver fibrosis in the absence of B cells. J. Clin. Invest., 2005, 115 (11), 3072-3082.
223. Marra, F.; Aleffi, S.; Galastri, S.; Provenzano, A. Mononuclear cells in liver fibrosis. Semin. Immunopathol., 2009, 31 (3), 345-358.
224. Petrarca, A.; Rigacci, L.; Monti, M.; Giannini, C.; Bernardi, F.; Caini, P.; Colagrande, S.; Bosi, A.; Laffi, G.; Zignego, A. L. Improvement in liver cirrhosis after treatment of HCV-related mixed cryoglobulinemia with rituximab. Dig. Liver Dis., 2007, 39 (Suppl 1), S129-33.
225. Moritoki, Y.; Zhang, W.; Tsuneyama, K.; Yoshida, K.; Wakabayashi, K.; Yang, G. X.; Bowlus, C.; Ridgway, W. M.; Ueno, Y.; Ansari, A. A.; Coppel, R. L.; Mackay, I. R.; Flavell, R. A.; Gershwin, M. E.; Lian, Z. X. B cells suppress the inflammatory response in a mouse model of primary biliary cirrhosis. Gastroenterology, 2009, 136 (3), 1037-1047.
226. Dhirapong, A.; Lleo, A.; Yang, G. X.; Tsuneyama, K.; Dunn, R.; Kehry, M.; Packard, T. A.; Cambier, J. C.; Liu, F. T.; Lindor, K.; Coppel, R. L.; Ansari, A. A.; Gershwin, M. E. B cell depletion therapy exacerbates murine primary biliary cirrhosis. Hepatology, 2010, 53 (2), 527-35.
227. Bigorgne, A. E.; Bouchet-Delbos, L.; Naveau, S.; Dagher, I.; Prevot, S.; Durand-Gasselin, I.; Couderc, J.; Valet, P.; Emilie, D.; Perlemuter, G. Obesity-induced lymphocyte hyperresponsiveness to chemokines: a new mechanism of Fatty liver inflammation in obese mice. Gastroenterology, 2008, 134 (5), 1459-1469.
228. Oliviero, B.; Cerino, A.; Varchetta, S.; Paudice, E.; Pai, S.; Ludovisi, S.; Zaramella, M.; Michelone, G.; Pugnale, P.; Negro, F.; Barnaba, V.; Mondelli, M. U. Enhanced B-cell differentiation and reduced proliferative capacity in chronic hepatitis C and chronic hepatitis B virus infections. J. Hepatol., 2011, 55 (1), 53-60.
229. Mizuochi, T.; Ito, M.; Saito, K.; Kasai, M.; Kunimura, T.; Morohoshi, T.; Momose, H.; Hamaguchi, I.; Takai, K.; Iino, S.; Suzuki, M.; Mochida, S.; Ikebuchi, K.; Yamaguchi, K. Possible recruitment of peripheral blood CXCR3+ CD27+ CD19+ B cells to the liver of chronic hepatitis C patients. J. Interferon. Cytokine Res., 2010, 30 (4), 243-252.
230. Spengler, U.; Nattermann, J. Immunopathogenesis in hepatitis C virus cirrhosis. Clin. Sci. (Lond), 2007, 112 (3), 141-55.
231. Safadi, R.; Ohta, M.; Alvarez, C. E.; Fiel, M. I.; Bansal, M.; Mehal, W. Z.; Friedman, S. L. Immune stimulation of hepatic fibrogenesis by CD8 cells and attenuation by transgenic interleukin-10 from hepatocytes. Gastroenterology, 2004, 127 (3), 870-882.
232. Muhanna, N.; Horani, A.; Doron, S.; Safadi, R. Lymphocyte-hepatic stellate cell proximity suggests a direct interaction. Clin. Exp. Immunol., 2007, 148 (2), 338-347.
233. Muhanna, N.; Doron, S.; Wald, O.; Horani, A.; Eid, A.; Pappo, O.; Friedman, S. L.; Safadi, R. Activation of hepatic stellate cells after phagocytosis of lymphocytes: A novel pathway of fibrogenesis. Hepatology, 2008, 48 (3), 963-977.
234. Schildberg, F. A.; Wojtalla, A.; Siegmund, S. V.; Endl, E.; Diehl, L.; Abdullah, Z.; Kurts, C.; Knolle, P. A. Murine hepatic stellate cells veto CD8 T cell activation by a CD54-dependent mechanism. Hepatology, 2011, 54 (1), 262-272.
235. Yang, G. X.; Lian, Z. X.; Chuang, Y. H.; Moritoki, Y.; Lan, R. Y.; Wakabayashi, K.; Ansari, A. A.; Flavell, R. A.; Ridgway, W. M.; Coppel, R. L.; Tsuneyama, K.; Mackay, I. R.; Gershwin, M. E. Adoptive transfer of CD8(+) T cells from transforming growth factor beta receptor type II (dominant negative form) induces autoimmune cholangitis in mice. Hepatology, 2008, 47 (6), 1974-1982.
236. Yang, G. X.; Wu, Y.; Tsukamoto, H.; Leung, P. S.; Lian, Z. X.; Rainbow, D. B.; Hunter, K. M.; Morris, G. A.; Lyons, P. A.; Peterson, L. B.; Wicker, L. S.; Gershwin, M. E.; Ridgway, W. M. CD8 T cells mediate direct biliary ductule damage in nonobese diabetic autoimmune biliary disease. J. Immunol., 2011, 186 (2), 1259-1267.
237. Kita, H.; Matsumura, S.; He, X. S.; Ansari, A. A.; Lian, Z. X.; Van de Water, J.; Coppel, R. L.; Kaplan, M. M.; Gershwin, M. E. Quantitative and functional analysis of PDC-E2-specific autoreactive cytotoxic T lymphocytes in primary biliary cirrhosis. J. Clin. Invest., 2002, 109 (9), 1231-1240.
238. Chiaramonte, M. G.; Donaldson, D. D.; Cheever, A. W.; Wynn, T. A. An IL-13 inhibitor blocks the development of hepatic fibrosis during a T-helper type 2-dominated inflammatory response. J. Clin. Invest., 1999, 104 (6), 777-785.
239. Sandler, N. G.; Mentink-Kane, M. M.; Cheever, A. W.; Wynn, T. A. Global gene expression profiles during acute pathogen-induced pulmonary inflammation reveal divergent roles for Th1 and Th2 responses in tissue repair. J. Immunol., 2003, 171 (7), 3655-3667.
240. Roderfeld, M.; Rath, T.; Pasupuleti, S.; Zimmermann, M.; Neumann, C.; Churin, Y.; Dierkes, C.; Voswinckel, R.; Barth, P. J.; Zahner, D.; Graf, J.; Roeb, E. Bone marrow transplantation improves hepatic fibrosis in Abcb4-/- mice via Th1 response and matrix metalloproteinase activity. Gut, 2011 [Epub ahead of print].
241. Farah, I. O.; Mola, P. W.; Kariuki, T. M.; Nyindo, M.; Blanton, R. E.; King, C. L. Repeated exposure induces periportal fibrosis in Schistosoma mansoni-infected baboons: role of TGF-beta and IL-4. J. Immunol., 2000, 164 (10), 5337-5343.
242. Cheever, A. W.; Williams, M. E.; Wynn, T. A.; Finkelman, F. D.; Seder, R. A.; Cox, T. M.; Hieny, S.; Caspar, P.; Sher, A. Anti-IL-4 treatment of Schistosoma mansoni-infected mice inhibits development of T cells and non-B, non-T cells expressing Th2 cytokines while decreasing egg-induced hepatic fibrosis. J. Immunol., 1994, 153 (2), 753-759.
243. Wynn, T. A.; Cheever, A. W.; Jankovic, D.; Poindexter, R. W.; Caspar, P.; Lewis, F. A.; Sher, A. An IL-12-based vaccination method for preventing fibrosis induced by schistosome infection. Nature, 1995, 376 (6541), 594-596.
244. Shi, Z.; Wakil, A. E.; Rockey, D. C. Strain-specific differences in mouse hepatic wound healing are mediated by divergent T helper cytokine responses. Proc. Natl. Acad Sci. USA, 1997, 94 (20), 10663-10668.
245. Weng, H. L.; Liu, Y.; Chen, J. L.; Huang, T.; Xu, L. J.; Godoy, P.; Hu, J. H.; Zhou, C.; Stickel, F.; Marx, A.; Bohle, R. M.; Zimmer, V.; Lammert, F.; Mueller, S.; Gigou, M.; Samuel, D.; Mertens, P. R.; Singer, M. V.; Seitz, H. K.; Dooley, S. The etiology of liver damage imparts cytokines transforming growth factor beta1 or interleukin-13 as driving forces in fibrogenesis. Hepatology, 2009, 50 (1), 230-243.
246. Hammerich, L.; Heymann, F.; Tacke, F. Role of IL-17 and Th17 cells in liver diseases. Clin. Dev. Immunol., 2011, 345803.
247. Wilson, M. S.; Madala, S. K.; Ramalingam, T. R.; Gochuico, B. R.; Rosas, I. O.; Cheever, A. W.; Wynn, T. A. Bleomycin and IL-1beta-mediated pulmonary fibrosis is IL-17A dependent. J. Exp. Med., 2010, 207 (3), 535-552.
248. Wei, H. X.; Chuang, Y. H.; Li, B.; Wei, H.; Sun, R.; Moritoki, Y.; Gershwin, M. E.; Lian, Z. X.; Tian, Z. CD4 CD25 Foxp3+ regulatory T cells protect against T cell-mediated fulminant hepatitis in a TGF-beta-dependent manner in mice. J. Immunol., 2008, 181 (10), 7221-7229.
249. Sturm, N.; Thelu, M. A.; Camous, X.; Dimitrov, G.; Ramzan, M.; Dufeu-Duchesne, T.; Bonorino, P.; Guillermet, C.; Brambilla, E.; Arvers, P.; Pernollet, M.; Leroy, V.; Zarski, J. P.; Marche, P. N.; Jouvin-Marche, E. Characterization and role of intra-hepatic regulatory T cells in chronic hepatitis C pathogenesis. J. Hepatol., 2010, 53 (1), 25-35.
250. Claassen, M. A.; de Knegt, R. J.; Tilanus, H. W.; Janssen, H. L.; Boonstra, A. Abundant numbers of regulatory T cells localize to the liver of chronic hepatitis C infected patients and limit the extent of fibrosis. J. Hepatol., 2010, 52 (3), 315-321.
251. Katz, S. C.; Ryan, K.; Ahmed, N.; Plitas, G.; Chaudhry, U. I.; Kingham, T. P.; Naheed, S.; Nguyen, C.; Somasundar, P.; Espat, N. J.; Junghans, R. P.; Dematteo, R. P. Obstructive jaundice expands intrahepatic regulatory T cells, which impair liver T lymphocyte function but modulate liver cholestasis and fibrosis. J. Immunol., 2011, 187 (3), 1150-1156.
252. Boisvert, J.; Kunkel, E. J.; Campbell, J. J.; Keeffe, E. B.; Butcher, E. C.; Greenberg, H. B. Liver-infiltrating lymphocytes in end-stage hepatitis C virus: subsets, activation status, and chemokine receptor phenotypes. J. Hepatol., 2003, 38 (1), 67-75.
253. Zeremski, M.; Petrovic, L. M.; Chiriboga, L.; Brown, Q. B.; Yee, H. T.; Kinkhabwala, M.; Jacobson, I. M.; Dimova, R.; Markatou, M.; Talal, A. H. Intrahepatic levels of CXCR3-associated chemokines correlate with liver inflammation and fibrosis in chronic hepatitis C. Hepatology, 2008, 48 (5), 1440-1450.
254. Harvey, C. E.; Post, J. J.; Palladinetti, P.; Freeman, A. J.; Ffrench, R. A.; Kumar, R. K.; Marinos, G.; Lloyd, A. R. Expression of the chemokine IP-10 (CXCL10) by hepatocytes in chronic hepatitis C virus infection correlates with histological severity and lobular inflammation. J. Leukoc. Biol., 2003, 74 (3), 360-369.
255. Helbig, K. J.; Ruszkiewicz, A.; Semendric, L.; Harley, H. A.; McColl, S. R.; Beard, M. R. Expression of the CXCR3 ligand I-TAC by hepatocytes in chronic hepatitis C and its correlation with hepatic inflammation. Hepatology, 2004, 39 (5), 1220-1229.
256. Apolinario, A.; Majano, P. L.; Alvarez-Perez, E.; Saez, A.; Lozano, C.; Vargas, J.; Garcia-Monzon, C. Increased expression of T cell chemokines and their receptors in chronic hepatitis C: relationship with the histological activity of liver disease. Am. J. Gastroenterol., 2002, 97 (11), 2861-2870.
257. Wasmuth, H. E.; Lammert, F.; Zaldivar, M. M.; Weiskirchen, R.; Hellerbrand, C.; Scholten, D.; Berres, M. L.; Zimmermann, H.; Streetz, K. L.; Tacke, F.; Hillebrandt, S.; Schmitz, P.; Keppeler, H.; Berg, T.; Dahl, E.; Gassler, N.; Friedman, S. L.; Trautwein, C. Antifibrotic effects of CXCL9 and its receptor CXCR3 in livers of mice and humans. Gastroenterology, 2009, 137 (1), 309-319, 319 e1-3.
258. Nakaya, I.; Wada, T.; Furuichi, K.; Sakai, N.; Kitagawa, K.; Yokoyama, H.; Ishida, Y.; Kondo, T.; Sugaya, T.; Kawachi, H.; Shimizu, F.; Narumi, S.; Haino, M.; Gerard, C.; Matsushima, K.; Kaneko, S. Blockade of IP-10/CXCR3 promotes progressive renal fibrosis. Nephron. Exp. Nephrol., 2007, 107 (1), e12-21.
259. Erhardt, A.; Wegscheid, C.; Claass, B.; Carambia, A.; Herkel, J.; Mittrucker, H. W.; Panzer, U.; Tiegs, G. CXCR3 deficiency exacerbates liver disease and abrogates tolerance in a mouse model of immune-mediated hepatitis. J. Immunol., 2011, 186 (9), 5284-5293.
260. Oo, Y. H.; Weston, C. J.; Lalor, P. F.; Curbishley, S. M.; Withers, D. R.; Reynolds, G. M.; Shetty, S.; Harki, J.; Shaw, J. C.; Eksteen, B.; Hubscher, S. G.; Walker, L. S.; Adams, D. H. Distinct roles for CCR4 and CXCR3 in the recruitment and positioning of regulatory T cells in the inflamed human liver. J. Immunol., 2010, 184 (6), 2886-2898.
261. Fadel, S. A.; Bromley, S. K.; Medoff, B. D.; Luster, A. D. CXCR3-deficiency protects influenza-infected CCR5-deficient mice from mortality. Eur J. Immunol., 2008, 38 (12), 3376-3387.
262. Miu, J.; Mitchell, A. J.; Muller, M.; Carter, S. L.; Manders, P. M.; McQuillan, J. A.; Saunders, B. M.; Ball, H. J.; Lu, B.; Campbell, I. L.; Hunt, N. H. Chemokine gene expression during fatal murine cerebral malaria and protection due to CXCR3 deficiency. J. Immunol., 2008, 180 (2), 1217-1230.
263. Schnickel, G. T.; Bastani, S.; Hsieh, G. R.; Shefizadeh, A.; Bhatia, R.; Fishbein, M. C.; Belperio, J.; Ardehali, A. Combined CXCR3/CCR5 blockade attenuates acute and chronic rejection. J. Immunol., 2008, 180 (7), 4714-4721.
264. Barbi, J.; Oghumu, S.; Rosas, L. E.; Carlson, T.; Lu, B.; Gerard, C.; Lezama-Davila, C. M.; Satoskar, A. R. Lack of CXCR3 delays the development of hepatic inflammation but does not impair resistance to Leishmania donovani. J. Infect. Dis., 2007, 195 (11), 1713-1717.
265. Chuang, Y. H.; Lian, Z. X.; Cheng, C. M.; Lan, R. Y.; Yang, G. X.; Moritoki, Y.; Chiang, B. L.; Ansari, A. A.; Tsuneyama, K.; Coppel, R. L.; Gershwin, M. E. Increased levels of chemokine receptor CXCR3 and chemokines IP-10 and MIG in patients with primary biliary cirrhosis and their first degree relatives. J. Autoimmun., 2005, 25 (2), 126-132.
266. Zhang, W.; Fei, Y.; Gao, J.; Liu, B.; Zhang, F. The role of CXCR3 in the induction of primary biliary cirrhosis. Clin. Dev. Immunol., 2011, 564062.
267. Holst, P. J.; Orskov, C.; Qvortrup, K.; Christensen, J. P.; Thomsen, A. R. CCR5 and CXCR3 are dispensable for liver infiltration, but CCR5 protects against virus-induced T-cell-mediated hepatic steatosis. J. Virol., 2007, 81 (18), 10101-10112.
268. Zaldivar, M. M.; Pauels, K.; von Hundelshausen, P.; Berres, M. L.; Schmitz, P.; Bornemann, J.; Kowalska, M. A.; Gassler, N.; Streetz, K. L.; Weiskirchen, R.; Trautwein, C.; Weber, C.; Wasmuth, H. E. CXC chemokine ligand 4 (Cxcl4) is a platelet-derived mediator of experimental liver fibrosis. Hepatology, 2010, 51 (4), 1345-1353.
269. Ajuebor, M. N.; Hogaboam, C. M.; Le, T.; Proudfoot, A. E.; Swain, M. G. CCL3/MIP-1alpha is pro-inflammatory in murine T cell-mediated hepatitis by recruiting CCR1-expressing CD4(+) T cells to the liver. Eur. J. Immunol., 2004, 34 (10), 2907-2918.
270. Larrubia, J. R.; Calvino, M.; Benito, S.; Sanz-de-Villalobos, E.; Perna, C.; Perez-Hornedo, J.; Gonzalez-Mateos, F.; Garcia-Garzon, S.; Bienvenido, A.; Parra, T. The role of CCR5/CXCR3 expressing CD8+ cells in liver damage and viral control during persistent hepatitis C virus infection. J. Hepatol., 2007, 47 (5), 632-641.
271. Shimizu, Y.; Murata, H.; Kashii, Y.; Hirano, K.; Kunitani, H.; Higuchi, K.; Watanabe, A. CC-chemokine receptor 6 and its ligand macrophage inflammatory protein 3alpha might be involved in the amplification of local necroinflammatory response in the liver. Hepatology, 2001, 34 (2), 311-319.
272. Xu, H. B.; Gong, Y. P.; Cheng, J.; Chu, Y. W.; Xiong, S. D., CXCL16 participates in pathogenesis of immunological liver injury by regulating T lymphocyte infiltration in liver tissue. World J. Gastroenterol., 2005, 11 (32), 4979-4985.
273. Fraticelli, P.; Sironi, M.; Bianchi, G.; D'Ambrosio, D.; Albanesi, C.; Stoppacciaro, A.; Chieppa, M.; Allavena, P.; Ruco, L.; Girolomoni, G.; Sinigaglia, F.; Vecchi, A.; Mantovani, A. Fractalkine (CX3CL1) as an amplification circuit of polarized Th1 responses. J. Clin. Invest., 2001, 107 (9), 1173-1181.
274. Isse, K.; Harada, K.; Zen, Y.; Kamihira, T.; Shimoda, S.; Harada, M.; Nakanuma, Y. Fractalkine and CX3CR1 are involved in the recruitment of intraepithelial lymphocytes of intrahepatic bile ducts. Hepatology, 2005, 41 (3), 506-516.
275. Sasaki, M.; Miyakoshi, M.; Sato, Y.; Nakanuma, Y. Modulation of the microenvironment by senescent biliary epithelial cells may be involved in the pathogenesis of primary biliary cirrhosis. J. Hepatol., 2010, 53 (2), 318-325.
276. Eksteen, B.; Miles, A.; Curbishley, S. M.; Tselepis, C.; Grant, A. J.; Walker, L. S.; Adams, D. H. Epithelial inflammation is associated with CCL28 production and the recruitment of regulatory T cells expressing CCR10. J. Immunol., 2006, 177 (1), 593-603.
277. Viola, A.; Luster, A. D. Chemokines and their receptors: drug targets in immunity and inflammation. Ann. Rev. Pharmacol. Toxicol., 2008, 48, 171-197.
278. Morales-Ibanez, O.; Bataller, R. Platelet-derived chemokines: new targets to treat liver fibrosis. J. Hepatol., 2011, 54 (3), 581-583.