In search of the magic bullet: Can liver inflammation and fibrosis be reversed with medications?

Expert Review of Gastroenterology and Hepatology

Volumn 9, Issue 9, 2015, Pages 1139-1141

  Zimmermann, Henning W ^a   Tacke, Frank ^a  

^a UNIVERSITY HOSPITAL RWTH AACHEN   (Germany)

Author keywords

Chemokine; Hepatic stellate cell; Liver fibrosis; Macrophages; Matrix; Regression

Indexed keywords

1 DEOXY 3 (1,1 DIMETHYLBUTYL) DELTA8 TETRAHYDROCANNABINOL; CANNABINOID 1 RECEPTOR; CANNABINOID 2 RECEPTOR; CENICRIVIROC; CHEMOKINE RECEPTOR CCR2; DIGESTIVE TRACT AGENT; GALECTIN 3; GR MD 01; GR MD 02; INTERLEUKIN 22; MNOX E36; MONOCYTE CHEMOTACTIC PROTEIN 1; MONOCYTE CHEMOTACTIC PROTEIN 1 INHIBITOR; SIMTUZUMAB; UNCLASSIFIED DRUG; ANTIINFLAMMATORY AGENT; GASTROINTESTINAL AGENT;

BONE MARROW DERIVED CELL TRANSFER; BONE MARROW DERIVED MACROPHAGE; CELL TRANSFER; CELLULAR BIAS SHIFTING; DIRECT MATRIX DEGRADATION; DRUG EFFICACY; DRUG SAFETY; DRUG TARGETING; HEPATITIS; HEPATITIS C; HUMAN; LIVER FIBROSIS; LIVER PROTECTION; MOLECULAR BIOLOGY; MYOFIBROBLAST; NONALCOHOLIC FATTY LIVER; NONHUMAN; PRIMARY SCLEROSING CHOLANGITIS; REVIEW; SIGNAL TRANSDUCTION; ANIMAL; LIVER CIRRHOSIS; METABOLISM; NON-ALCOHOLIC FATTY LIVER DISEASE;

ANIMALS; ANTI-INFLAMMATORY AGENTS; GASTROINTESTINAL AGENTS; HUMANS; LIVER CIRRHOSIS; NON-ALCOHOLIC FATTY LIVER DISEASE;

EID: 84939784691     PISSN: 17474124     EISSN: 17474132     Source Type: Journal    
DOI: 10.1586/17474124.2015.1063417     Document Type: Review

References (26)

1. Ellis EL, Mann DA. Clinical evidence for the regression of liver fibrosis. J Hepatol 2012;56(5):1171-80
2. Marcellin P, Gane E, Buti M, et al. Regression of cirrhosis during treatment with tenofovir disoproxil fumarate for chronic hepatitis B: a 5-year open-label follow-up study. Lancet 2013;381(9865):468-75
3. Schuppan D, Kim YO. Evolving therapies for liver fibrosis. J Clin Invest 2013;123(5): 1887-901
4. Pellicoro A, Ramachandran P, Iredale JP, et al. Liver fibrosis and repair: immune regulation of wound healing in a solid organ. Nat Review Immunol 2014;14(3):181-94
5. Tacke F, Trautwein C. Mechanisms of liver fibrosis resolution. J Hepatol 2015; in press
6. Duffield JS, Forbes SJ, Constandinou CM, et al. Selective depletion of macrophages reveals distinct, opposing roles during liver injury and repair. J Clin Invest 2005; 115(1):56-65
7. Tacke F, Zimmermann HW. Macrophage heterogeneity in liver injury and fibrosis. J Hepatol 2014;60(5):1090-6
8. Ehling J, Bartneck M, Wei X, et al. CCL2-dependent infiltrating macrophages promote angiogenesis in progressive liver fibrosis. Gut 2014;63(12):1960-71
9. Kantari-Mimoun C, Castells M, Klose R, et al. Resolution of liver fibrosis requires myeloid cell-driven sinusoidal angiogenesis. Hepatology 2015;61(6):2042-55
10. Ramachandran P, Pellicoro A, Vernon MA, et al. Differential Ly-6C expression identifies the recruited macrophage phenotype, which orchestrates the regression of murine liver fibrosis. Proc Natl Acad Sci USA 2012;109(46):E3186-95
11. Thomas JA, Pope C, Wojtacha D, et al. Macrophage therapy for murine liver fibrosis recruits host effector cells improving fibrosis, regeneration, and function. Hepatology 2011;53(6):2003-15
12. Higashiyama R, Inagaki Y, Hong YY, et al. Bone marrow-derived cells express matrix metalloproteinases and contribute to regression of liver fibrosis in mice. Hepatology 2007;45(1):213-22
13. Issa R, Zhou X, Constandinou CM, et al. Spontaneous recovery from micronodular cirrhosis: evidence for incomplete resolution associated with matrix cross-linking. Gastroenterol 2004;126(7):1795-808
14. Bartneck M, Scheyda KM, Warzecha KT, et al. Fluorescent cell-traceable dexamethasone-loaded liposomes for the treatment of inflammatory liver diseases. Biomaterials 2015;37:367-82
15. Baeck C, Wei X, Bartneck M, et al. Pharmacological inhibition of the chemokine C-C motif chemokine ligand 2 (monocyte chemoattractant protein 1) accelerates liver fibrosis regression by suppressing Ly-6C(+) macrophage infiltration in mice. Hepatology 2014;59(3):1060-72
16. Baeck C, Wehr A, Karlmark KR, et al. Pharmacological inhibition of the chemokine CCL2 (MCP-1) diminishes liver macrophage infiltration and steatohepatitis in chronic hepatic injury. Gut 2012;61(3):416-26
17. Berres ML, Koenen RR, Rueland A, et al. Antagonism of the chemokine Ccl5 ameliorates experimental liver fibrosis in mice. J Clin Invest 2010;120(11): 4129-40
18. Li LC, Li J, Gao J. Functions of galectin-3 and its role in fibrotic diseases. J Pharmacol Exp Ther 2014;351(2):336-43
19. Traber PG, Chou H, Zomer E, et al. Regression of fibrosis and reversal of cirrhosis in rats by galectin inhibitors in thioacetamide-induced liver disease. PLoS One 2013;8(10):e75361
20. Coombes JD, Swiderska-Syn M, Dolle L, et al. Osteopontin neutralisation abrogates the liver progenitor cell response and fibrogenesis in mice. Gut 2015;64(7):1120-31
21. Hammerich L, Bangen JM, Govaere O, et al. Chemokine receptor CCR6-dependent accumulation of gammadelta T cells in injured liver restricts hepatic inflammation and fibrosis. Hepatology 2014;59(2):630-42
22. Kong X, Feng D, Wang H, et al. Interleukin-22 induces hepatic stellate cell senescence and restricts liver fibrosis in mice. Hepatology 2012;56(3):1150-9.2012
23. Sertorio M, Hou X, Carmo RF, et al. IL-22 and IL-22 binding protein (IL-22BP) regulate fibrosis and cirrhosis in hepatitis C virus and schistosome infections. Hepatology 2015;61(4):1321-31
24. Mallat A, Teixeira-Clerc F, Lotersztajn S. Cannabinoid signaling and liver therapeutics. J Hepatol 2013;59(4):891-6
25. Tam J, Vemuri VK, Liu J, et al. Peripheral CB1 cannabinoid receptor blockade improves cardiometabolic risk in mouse models of obesity. J Clin Invest 2010;120(8):2953-66
26. Barry-Hamilton V, Spangler R, Marshall D, et al. Allosteric inhibition of lysyl oxidase-like-2 impedes the development of a pathologic microenvironment. Nat Med 2010;16(9):1009-17