Bacteria- and host-derived mechanisms to control intestinal epithelial cell homeostasis: Implications for chronic inflammation

Inflammatory Bowel Diseases

Volumn 13, Issue 9, 2007, Pages 1153-1164

  Clavel, Thomas ^a   Haller, Dirk ^a  

^a TECHNICAL UNIVERSITY OF MUNICH   (Germany)

Author keywords

Commensal bacteria; Endoplasmic reticulum stress; Glucose regulated protein (Grp) 78; Host derived anti inflammatory signals; Inflammatory bowel diseases; Interleukin 10; Intestinal epithelial cells; Nuclear transcription factor B (NF B)

Indexed keywords

ANTISENSE OLIGONUCLEOTIDE; GLUCOSE REGULATED PROTEIN 78; I KAPPA B; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 10; NUCLEOTIDE BINDING PROTEIN; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; TOLL LIKE RECEPTOR; TRANSFORMING GROWTH FACTOR BETA;

ADAPTIVE IMMUNITY; CROHN DISEASE; DISEASE COURSE; DRUG MECHANISM; ENDOPLASMIC RETICULUM STRESS; ENTERITIS; ENVIRONMENTAL FACTOR; FEEDBACK SYSTEM; GENETIC PREDISPOSITION; HOMEOSTASIS; HOST RESISTANCE; HUMAN; INNATE IMMUNITY; INTESTINE EPITHELIUM CELL; INTESTINE FLORA; MUCOSAL IMMUNITY; NONHUMAN; OLIGOMERIZATION; PREVALENCE; PRIORITY JOURNAL; PROTEIN DOMAIN; PROTEIN EXPRESSION; REVIEW; SIGNAL TRANSDUCTION; ULCERATIVE COLITIS;

ANIMALS; ANTI-INFLAMMATORY AGENTS; ENDOPLASMIC RETICULUM; EPITHELIAL CELLS; FEEDBACK, BIOCHEMICAL; GENETIC PREDISPOSITION TO DISEASE; HEAT-SHOCK PROTEINS; HUMANS; INFLAMMATION; INFLAMMATORY BOWEL DISEASES; INTERLEUKIN-10; MOLECULAR CHAPERONES; NF-KAPPA B; PROTEIN STRUCTURE, TERTIARY; TOLL-LIKE RECEPTORS; TRANSFORMING GROWTH FACTOR BETA;

EID: 34548612724     PISSN: 10780998     EISSN: 15364844     Source Type: Journal    
DOI: 10.1002/ibd.20174     Document Type: Review

References (155)

1. Hugot JP, Chamaillard M, Zouali H, et al. Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease. Nature. 2001;411:599-603.
2. Ogura Y, Bonen DK, Inohara N, et al. A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease. Nature. 2001;411: 603-606.
3. McGovern DP, Hysi P, Ahmad T, et al. Association between a complex insertion/deletion polymorphism in NOD1 (CARD4) and susceptibility to inflammatory bowel disease. Hum Mol Genet. 2005;14:1245-1250.
4. Franchimont D, Vermeire S, El Housni H, et al. Deficient host-bacteria interactions in inflammatory bowel disease? The toll-like receptor (TLR)-4 Asp299gly polymorphism is associated with Crohn's disease and ulcerative colitis. Gut. 2004;53:987-992.
5. Torok HP, Glas J, Tonenchi L, et al. Crohn's disease is associated with a toll-like receptor-9 polymorphism. Gastroenterology. 2004;127:365-366.
6. Peltekova VD, Wintle RF, Rubin LA, et al. Functional variants of OCTN cation transporter genes are associated with Crohn disease. Nat Genet. 2004;36:471-475.
7. Rioux JD, Daly MJ, Silverberg MS, et al. Genetic variation in the 5q31 cytokine gene cluster confers susceptibility to Crohn disease. Nat Genet. 2001;29:223-228.
8. Brant SR, Panhuysen CI, Nicolae D, et al. MDR1 Ala893 polymorphism is associated with inflammatory bowel disease. Am J Hum Genet. 2003;73:1282-1292.
9. Schwab M, Schaeffeler E, Marx C, et al. Association between the C3435T MDR1 gene polymorphism and susceptibility for ulcerative colitis. Gastroenterology. 2003;124:26-33.
10. Hampe J, Franke A, Rosenstiel P, et al. A genome-wide association scan of nonsynonymous SNPs identifies a susceptibility variant for Crohn disease in ATG16L1. Nat Genet. 2007;39:207-211.
11. Stoll M, Corneliussen B, Costello CM, et al. Genetic variation in DLG5 is associated with inflammatory bowel disease. Nat Genet. 2004;36: 476-480.
12. Yamazaki K, McGovern D, Ragoussis J, et al. Single nucleotide polymorphisms in TNFSF15 confer susceptibility to Crohn's disease. Hum Mol Genet. 2005;14:3499-3506.
13. Duerr RH, Taylor KD, Brant SR, et al. A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science. 2006;314:1461-1463.
14. Halfvarson J, Bodin L, Tysk C, et al. Inflammatory bowel disease in a Swedish twin cohort: a long-term follow-up of concordance and clinical characteristics. Gastroenterology. 2003;124:1767-1773.
15. Lakatos PL. Recent trends in the epidemiology of inflammatory bowel diseases: up or down? World J Gastroenterol. 2006;12:6102-6108.
16. Rutgeerts P, Goboes K, Peeters M, et al. Effect of faecal stream diversion on recurrence of Crohn's disease in the neoterminal ileum. Lancet. 1991;338:771-774.
17. D'Haens GR, Geboes K, Peeters M, et al. Early lesions of recurrent Crohn's disease caused by infusion of intestinal contents in excluded ileum. Gastroenterology. 1998;114:262-267.
18. Onderdonk AB, Franklin ML, Cisneros RL. Production of experimental ulcerative colitis in gnotobiotic guinea pigs with simplified microflora. Infect Immun. 1981;32:225-231.
19. Rath HC, Wilson KH, Sartor RB. Differential induction of colitis and gastritis in HLA-B27 transgenic rats selectively colonized with Bacteroides vulgatus or Escherichia coli. Infect Immun. 1999;67:2969-2974.
20. Waidmann M, Bechtold O, Frick JS, et al. Bacteroides vulgatus protects against Escherichia coli-induced colitis in gnotobiotic interleukin-2-deficient mice. Gastroenterology. 2003;125:162-177.
21. Sellon RK, Tonkonogy S, Schultz M, et al. Resident enteric bacteria are necessary for development of spontaneous colitis and immune system activation in interleukin-10-deficient mice. Infect Immun. 1998;66: 5224-5231.
22. Kim SC, Tonkonogy SL, Albright CA, et al. Variable phenotypes of enterocolitis in interleukin 10-deficient mice monoassociated with two different commensal bacteria. Gastroenterology. 2005;128:891-906.
23. Sartor RB. Does Mycobacterium avium subspecies paratuberculosis cause Crohn's disease? Gut. 2005;54:896-898.
24. Darfeuille-Michaud A, Boudeau J, Bulois P, et al. High prevalence of adherent-invasive Escherichia coli associated with ileal mucosa in Crohn's disease. Gastroenterology. 2004;127:412-421.
25. Manichanh C, Rigottier-Gois L, Bonnaud E, et al. Reduced diversity of faecal microbiota in Crohn's disease revealed by a metagenomic approach. Gut. 2006;55:205-211.
26. Swidsinski A, Ladhoff A, Pernthaler A, et al. Mucosal flora in inflammatory bowel disease. Gastroenterology. 2002;122:44-54.
27. Furrie E, Macfarlane S, Cummings JH, et al. Systemic antibodies towards mucosal bacteria in ulcerative colitis and Crohn's disease differentially activate the innate immune response. Gut. 2004;53:91-98.
28. Rembacken BJ, Snelling AM, Hawkey PM, et al. Non-pathogenic Escherichia coli versus mesalazine for the treatment of ulcerative colitis: a randomised trial. Lancet. 1999;354:635-639.
29. Grabig A, Paclik D, Guzy C, et al. Escherichia coli strain Nissle 1917 ameliorates experimental colitis via toll-like receptor 2- and toll-like receptor 4-dependent pathways. Infect Immun. 2006;74:4075-4082.
30. Gionchetti P, Rizzello F, Helwig U, et al. Prophylaxis of pouchitis onset with probiotic therapy: a double-blind, placebo-controlled trial. Gastroenterology. 2003;124:1202-1209.
31. Gionchetti P, Rizzello F, Venturi A, et al. Oral bacteriotherapy as maintenance treatment in patients with chronic pouchitis: a double-blind, placebo-controlled trial. Gastroenterology. 2000;119:305-309.
32. Di Giacinto C, Marinaro M, Sanchez M, et al. Probiotics ameliorate recurrent Th1-mediated murine colitis by inducing IL-10 and IL-10-dependent TGF-beta-bearing regulatory cells. J Immunol. 2005;174: 3237-3246.
33. Madsen K, Cornish A, Soper P, et al. Probiotic bacteria enhance murine and human intestinal epithelial barrier function. Gastroenterology. 2001;121:580-591.
34. Rachmilewitz D, Katakura K, Karmeli F, et al. Toll-like receptor 9 signaling mediates the anti-inflammatory effects of probiotics in murine experimental colitis. Gastroenterology. 2004;126:520-528.
35. Eckburg PB, Bik EM, Bernstein CN, et al. Diversity of the human intestinal microbial flora. Science. 2005;308:1635-1638.
36. Cebra JJ. Influences of microbiota on intestinal immune system development. Am J Clin Nutr. 1999;69:1046S-1051S.
37. Perez PF, Dore J, Leclerc M, et al. Bacterial imprinting of the neonatal immune system: lessons from maternal cells? Pediatrics. 2007;119: e724-732.
38. Kraus TA, Toy L, Chan L, et al. Failure to induce oral tolerance to a soluble protein in patients with inflammatory bowel disease. Gastroenterology. 2004;26:1771-1778.
39. Duchmann R, Kaiser I, Hermann E, et al. Tolerance exists towards resident intestinal flora but is broken in active inflammatory bowel disease (IBD). Clin Exp Immunol. 1995;102:448-455.
40. Takahashi K, Ip WE, Michelow IC, et al. The mannose-binding lectin: a prototypic pattern recognition molecule. Curr Opin Immunol. 2006; 18:16-23.
41. He YW, Li H, Zhang J, et al. The extracellular matrix protein mindin is a pattern-recognition molecule for microbial pathogens. Nat Immunol. 2004;5:88-97.
42. Cario E. Bacterial interactions with cells of the intestinal mucosa: Toll-like receptors and NOD2. Gut. 2005;54:1182-1193.
43. Iwasaki A, Medzhitov R. Toll-like receptor control of the adaptive immune responses. Nat Immunol. 2004;5:987-995.
44. Akira S, Takeda K. Toll-like receptor signalling. Nat Rev Immunol. 2004;4:499-511.
45. Rakoff-Nahoum S, Hao L, Medzhitov R. Role of Toll-like receptors in spontaneous commensal-dependent colitis. Immunity. 2006;25:319-329.
46. Rakoff-Nahoum S, Paglino J, Eslami-Varzaneh F, et al. Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis. Cell. 2004;118:229-241.
47. Sundberg JP, Elson CO, Bedigian H, et al. Spontaneous, heritable colitis in a new substrain of C3H/HeJ mice. Gastroenterology. 1994; 107:1726-1735.
48. Mahler M, Bristol IJ, Leiter EH, et al. Differential susceptibility of inbred mouse strains to dextran sulfate sodium-induced colitis. Am J Physiol. 1998;274:G544-551.
49. Bashir ME, Louie S, Shi HN, et al. Toll-like receptor 4 signaling by intestinal microbes influences susceptibility to food allergy. J Immunol. 2004;172:6978-6987.
50. Katakura K, Lee J, Rachmilewitz D, et al. Toll-like receptor 9-induced type I IFN protects mice from experimental colitis. J Clin Invest. 2005;115:695-702.
51. Lee J, Mo JH, Katakura K, et al. Maintenance of colonic homeostasis by distinctive apical TLR9 signalling in intestinal epithelial cells. Nat Cell Biol. 2006;8:1327-1336.
52. Schnare M, Barton GM, Holt AC, et al. Toll-like receptors control activation of adaptive immune responses. Nat Immunol. 2001;2:947-950.
53. Carneiro LA, Travassos LH, Philpott DJ. Innate immune recognition of microbes through Nod1 and Nod2: implications for disease. Microbes Infect. 2004;6:609-616.
54. Barnich N, Hisamatsu T, Aguirre JE, et al. GRIM-19 interacts with nucleotide oligomerization domain 2 and serves as downstream effector of anti-bacterial function in intestinal epithelial cells. J Biol Chem. 2005;280:19021-19026.
55. McDonald C, Chen FF, Ollendorff V, et al. A role for Erbin in the regulation of Nod2-dependent NF-kappaB signaling. J Biol Chem. 2005;280:40301-40309.
56. Kobayashi KS, Chamaillard M, Ogura Y, et al. Nod2-dependent regulation of innate and adaptive immunity in the intestinal tract. Science. 2005;307:731-734.
57. Newman B, Siminovitch KA. Recent advances in the genetics of inflammatory bowel disease. Curr Opin Gastroenterol. 2005;21:401-407.
58. Lodes MJ, Cong Y, Elson CO, et al. Bacterial flagellin is a dominant antigen in Crohn disease. J Clin Invest. 2004;113:1296-1306.
59. Targan SR, Landers CJ, Yang H, et al. Antibodies to CBir1 flagellin define a unique response that is associated independently with complicated Crohn's disease. Gastroenterology. 2005;128:2020-2028.
60. Papadakis KA, Yang H, Ippoliti A, et al. Anti-flagellin (CBir1) phenotypic and genetic Crohn's disease associations. Inflamm Bowel Dis. 2007;13:524-530.
61. Wehkamp J, Harder J, Weichenthal M, et al. NOD2 (CARD15) mutations in Crohn's disease are associated with diminished mucosal alpha-defensin expression. Gut. 2004;53:1658-1664.
62. Maeda S, Hsu LC, Liu H, et al. Nod2 mutation in Crohn's disease potentiates NF-kappaB activity and IL-1beta processing. Science. 2005;307:734-738.
63. Watanabe T, Kitani A, Murray PJ, et al. NOD2 is a negative regulator of Toll-like receptor 2-mediated T helper type 1 responses. Nat Immunol. 2004;5:800-808.
64. Pauleau AL, Murray PJ. Role of nod2 in the response of macrophages to toll-like receptor agonists. Mol Cell Biol. 2003;23:7531-7539.
65. Hugot JP, Zaccaria I, Cavanaugh J, et al. Prevalence of CARD15/NOD2 mutations in Caucasian healthy people. Am J Gastroenterol. 2007 (in press).
66. Framson PE, Cho DH, Lee LY, et al. Polarized expression and function of the costimulatory molecule CD58 on human intestinal epithelial cells. Gastroenterology. 1999;116:1054-1062.
67. Hershberg RM, Framson PE, Cho DH, et al. Intestinal epithelial cells use two distinct pathways for HLA class II antigen processing. J Clin Invest. 1997;100:204-215.
68. Campbell NA, Kim HS, Blumberg RS, et al. The nonclassical class I molecule CD1d associates with the novel CDS ligand gp180 on intestinal epithelial cells. J Biol Chem. 1999;274:26259-26265.
69. Abreu MT, Fukata M, Arditi M. TLR signaling in the gut in health and disease. J Immunol. 2005;174:4453-4460.
70. Hisamatsu T, Suzuki M, Reinecker HC, et al. CARD15/NOD2 functions as an antibacterial factor in human intestinal epithelial cells. Gastroenterology. 2003;124:993-1000.
71. Yang SK, Eckmann L, Panja A, et al. Differential and regulated expression of C-X-C, C-C, and C-chemokines by human colon epithelial cells. Gastroenterology. 1997;113:1214-1223.
72. Wehkamp J, Schmid M, Fellermann K, et al. Defensin deficiency, intestinal microbes, and the clinical phenotypes of Crohn's disease. J Leukoc Biol. 2005;77:460-465.
73. Cash HL, Whitham CV, Behrendt CL, et al. Symbiotic bacteria direct expression of an intestinal bactericidal lectin. Science. 2006;313:1126-1130.
74. Pahl HL. Activators and target genes of Rel/NF-κB transcription factors. Oncogene. 1999;18:5853-6866.
75. Niess JH, Brands, Gu X, et al. CX3CR1-mediated dendritic cell access to the intestinal lumen and bacterial clearance. Science. 2005;307:254-258.
76. Neutra MR, Mantis NJ, Kraehenbuhl JP. Collaboration of epithelial cells with organized mucosal lymphoid tissues. Nat Immunol. 2001;2: 1004-1009.
77. Gonzalez-Rey E, Delgado M. Therapeutic treatment of experimental colitis with regulatory dendritic cells generated with vasoactive intestinal peptide. Gastroenterology. 2006;131:1799-1811.
78. Fuss IJ, Neurath M, Boirivant M, et al. Disparate CD4+ lamina propria (LP) lymphokine secretion profiles in inflammatory bowel disease. Crohn's disease LP cells manifest increased secretion of IFN-gamma, whereas ulcerative colitis LP cells manifest increased secretion of IL-5. J Immunol. 1996;157:1261-1270.
79. Hart AL, Al-Hassi HO, Rigby RJ, et al. Characteristics of intestinal dendritic cells in inflammatory bowel diseases. Gastroenterology. 2005;129:50-65.
80. Rimoldi M, Chieppa M, Salucci V, et al. Intestinal immune homeostasis is regulated by the crosstalk between epithelial cells and dendritic cells. Nat Immunol. 2005;6:507-514.
81. Olson TS, Reuter BK, Scott KG, et al. The primary defect in experimental ileitis originates from a nonhematopoietic source. J Exp Med. 2006;203:541-552.
82. Katz KD, Hollander D, Vadheim CM, et al. Intestinal permeability in patients with Crohn's disease and their healthy relatives. Gastroenterology. 1989;97:927-931.
83. Hausmann M, Kiessling S, Mestermann S, et al. Toll-like receptors 2 and 4 are up-regulated during intestinal inflammation. Gastroenterology. 2002;122:1987-2000.
84. Rogler G, Brand K, Vogl D, et al. Nuclear factor κB is activated in macrophages and epithelial cells of inflamed intestinal mucosa. Gastroenterology. 1998;115:357-369.
85. Neurath M, Pettersson S, Meyer Zum Buschenfelde K-H, et al. Local administration of antisense phosphothioate oligonucleotides to the p65 subunit of NF-κB abrogates established experimental colitis in mice. Nat Med. 1996;2:998-1004.
86. Lawrence T, Gilroy DW, Colville-Nash PR, et al. Possible new role for NF-kappaB in the resolution of inflammation. Nat Med. 2001;7:1291-1297.
87. Egan LJ, de Lecea A, Lehrman ED, et al. Nuclear factor-kappa B activation promotes restitution of wounded intestinal epithelial monolayers. Am J Physiol Cell Physiol. 2003;285:C1028-1035.
88. Chen LW, Egan L, Li ZW, et al. The two faces of IKK and NF-kappaB inhibition: prevention of systemic inflammation but increased local injury following intestinal ischemia-reperfusion. Nat Med. 2003;9:575-581.
89. Ruiz PA, Shkoda A, Kim SC, et al. IL-10 gene-deficient mice lack TGF-beta/Smad signaling and fail to inhibit proinflammatory gene expression in intestinal epithelial cells after the colonization with colitogenic Enterococcus faecalis. J Immunol. 2005;174:2990-2999.
90. Fusunyan RD, Nanthakumar NN, Baldeon ME, et al. Evidence for an innate immune response in the immature human intestine: toll-like receptors on fetal enterocytes. Pediatr Res. 2001;49:589-593.
91. Haller D, Russo MP, Sartor RB, et al. IKK beta and phosphatidylinositol 3-kinase/Akt participate in non-pathogenic Gram-negative enteric bacteria-induced RelA phosphorylation and NF-kappa B activation in both primary and intestinal epithelial cell lines. J Biol Chem. 2002; 277:38168-38178.
92. Haller D, Holt L, Kim SC, et al. Transforming growth factor-beta1 inhibits non-pathogenic Gram negative bacteria-induced NF-kappaB recruitment to the interleukin-6 gene promoter in intestinal epithelial cells through modulation of histone acetylation. J Biol Chem. 2003; 278:23851-23860.
93. Ruiz PA, Kim SC, Sartor RB, et al. 15-Deoxy-delta12,14-prostaglandin J2-mediated ERK signaling inhibits Gram-negative bacteria-induced RelA phosphorylation and interleukin-6 gene expression in intestinal epithelial cells through modulation of protein phosphatase 2A activity. J Biol Chem. 2004;279:36103-36111.
94. Hornef MW, Frisan T, Vandewalle A, et al. Toll-like receptor 4 resides in the Golgi apparatus and colocalizes with internalized lipopolysaccharide in intestinal epithelial cells. J Exp Med. 2002;195:559-570.
95. Lotz M, Gutle D, Walther S, et al. Postnatal acquisition of endotoxin tolerance in intestinal epithelial cells. J Exp Med. 2006;203:973-984.
96. Visekruna A, Joeris T, Seidel D, et al. Proteasome-mediated degradation of IkappaBalpha and processing of p105 in Crohn disease and ulcerative colitis. J Clin Invest. 2006;116:3195-3203.
97. Ruiz PA, Hoffmann M, Szcesny S, et al. Innate mechanisms for Bifidobacterium lactis to activate transient pro-inflammatory host responses in intestinal epithelial cells after the colonization of germ-free rats. Immunology. 2005;115:441-450.
98. Boone DL, Turer EE, Lee EG, et al. The ubiquitin-modifying enzyme A20 is required for termination of Toll-like receptor responses. Nat Immunol. 2004;5:1052-1060.
99. Kobayashi K, Hernandez LD, Galan JE, et al. IRAK-M is a negative regulator of Toll-like receptor signaling. Cell. 2002;110:191-202.
100. Brint EK, Xu D, Liu H, et al. ST2 is an inhibitor of interleukin 1 receptor and Toll-like receptor 4 signaling and maintains endotoxin tolerance. Nat Immunol. 2004;5:373-379.
101. Wald D, Qin J, Zhao Z, et al. SIGIRR, a negative regulator of Toll-like receptor-interleukin 1 receptor signaling. Nat Immunol. 2003;4:920-927.
102. Zhang G, Ghosh S. Negative regulation of toll-like receptor-mediated signaling by Tollip. J Biol Chem. 2002;277:7059-7065.
103. Chuang TH, Ulevitch RJ. Triad3A, an E3 ubiquitin-protein ligase regulating Toll-like receptors. Nat Immunol. 2004;5:495-502.
104. Garlanda C, Riva F, Polentarutti N, et al. Intestinal inflammation in mice deficient in Tir8, an inhibitory member of the IL-1 receptor family. Proc Natl Acad Sci U S A. 2004;101:3522-3526.
105. Otte JM, Cario E, Podolsky DK. Mechanisms of cross hyporesponsiveness to Toll-like receptor bacterial ligands in intestinal epithelial cells. Gastroenterology. 2004;126:1054-1070.
106. Melmed G, Thomas LS, Lee N, et al. Human intestinal epithelial cells are broadly unresponsive to Toll-like receptor 2-dependent bacterial ligands: implications for host-microbial interactions in the gut. J Immunol. 2003;170:1406-1415.
107. Daynes RA, Jones DC. Emerging roles of PPARs in inflammation and immunity. Nat Rev Immunol. 2002;2:748-759.
108. Fajas L, Auboeuf D, Raspe E, et al. The organization, promoter analysis, and expression of the human PPARgamma gene. J Biol Chem. 1997;272:18779-18789.
109. Sugawara K, Olson TS, Moskaluk CA, et al. Linkage to peroxisome proliterator-activated receptor-gamma in SAMP1/YitFc mice and in human Crohn's disease. Gastroenterology. 2005;128:351-360.
110. Dubuquoy L, Jansson EA, Deeb S, et al. Impaired expression of peroxisome proliferator-activated receptor gamma in ulcerative colitis. Gastroenterology. 2003;124:1265-1276.
111. Katayama K, Wada K, Nakajima A, et al. A novel PPAR gamma gene therapy to control inflammation associated with inflammatory bowel disease in a murine model. Gastroenterology. 2003;124:1315-1324.
112. Desreumaux P, Dubuquoy L, Nutten S, et al. Attenuation of colon inflammation through activators of the retinoid X receptor (RXR)/peroxisome proliferator-activated receptor gamma (PPARgamma) heterodimer. A basis for new therapeutic strategies. J Exp Med. 2001;193: 827-838.
113. Kelly D, Campbell JI, King TP, et al. Commensal anaerobic gut bacteria attenuate inflammation by regulating nuclear-cytoplasmic shuttling of PPAR-gamma and RelA. Nat Immunol. 2004;5:104-112.
114. Janssens V, Goris J. Protein phosphatase 2A: a highly regulated family of serine/threonine phosphatases implicated in cell growth and signalling. Biochem J. 2001;353:417-439.
115. Brown SL, Riehl TE, Walker MR, et al. Myd88-dependent positioning of Ptgs2-expressing stromal cells maintains colonic epithelial proliferation during injury. J Clin Invest. 2007;117:258-269.
116. Powrie F, Correa-Oliveira R, Mauze S, et al. Regulatory interactions between CD45RBhigh and CD45RBlow CD4+ T cells are important for the balance between protective and pathogenic cell-mediated immunity. J Exp Med. 1994;179:589-600.
117. Maloy KJ, Salaun L, Cahill R, et al. CD4+CD25+ T(R) cells suppress innate immune pathology through cytokine-dependent mechanisms. J Exp Med. 2003;197:111-119.
118. Berg DJ, Davidson N, Kuhn R, et al. Enterocolitis and colon cancer in interleukin-10-deficient mice are associated with aberrant cytokine production and CD4(+) TH1-like responses. J Clin Invest. 1996;98: 1010-1020.
119. Fuss IJ, Boirivant M, Lacy B, et al. The interrelated roles of TGF-beta and IL-10 in the regulation of experimental colitis. J Immunol. 2002; 168:900-908.
120. Kulkarni AB, Ward JM, Yaswen L, et al. Transforming growth factor-beta 1 null mice. An animal model for inflammatory disorders. Am J Pathol. 1995;146:264-275.
121. Kitani A, Fuss IJ, Nakamura K, et al. Treatment of experimental (Trinitrobenzene sulfonic acid) colitis by intranasal administration of transforming growth factor (TGF)-beta1 plasmid: TGF-beta1-mediated suppression of T helper cell type 1 response occurs by interleukin (IL)-10 induction and IL-12 receptor beta2 chain downregulation. J Exp Med. 2000;192:41-52.
122. Hahm KB, Im YH, Parks TW, et al. Loss of transforming growth factor beta signalling in the intestine contributes to tissue injury in inflammatory bowel disease. Gut. 2001;49:190-198.
123. Shi Y, Massague J. Mechanisms of TGF-beta signaling from cell membrane to the nucleus. Cell. 2003;113:685-700.
124. Monteleone G, Del Vecchio Blanco G, Monteleone I, et al. Posttranscriptional regulation of Smad7 in the gut of patients with inflammatory bowel disease. Gastroenterology. 2005;129:1420-1429.
125. Boirivant M, Pallone F, Di Giacinto C, et al. Inhibition of Smad7 with a specific antisense oligonucleotide facilitates TGF-beta1-mediated suppression of colitis. Gastroenterology. 2006;131:1786-1798.
126. Rutkowski DT, Kaufman RJ. A trip to the ER: coping with stress. Trends Cell Biol. 2004;14:20-28.
127. Pahl HL. Signal transduction from the endoplasmic reticulum to the cell nucleus. Physiol Rev. 1999;79:683-701.
128. Rutkowski DT, Arnold SM, Miller CN, et al. Adaptation to ER stress is mediated by differential stabilities of pro-survival and pro-apoptotic mRNAs and proteins. PLoS Biol. 2006;4:e374.
129. Szegezdi E, Logue SE, Gorman AM, et al. Mediators of endoplasmic reticulum stress-induced apoptosis. EMBO Rep. 2006;7:880-885.
130. Hu P, Han Z, Couvillon AD, et al. Autocrine tumor necrosis factor alpha links endoplasmic reticulum stress to the membrane death receptor pathway through IRE1alpha-mediated NF-kappaB activation and down-regulation of TRAF2 expression. Mol Cell Biol. 2006;26:3071-3084.
131. Yoshida H. ER stress and diseases. FEBS J. 2007;274:630-658.
132. Zhao L, Ackerman SL. Endoplasmic reticulum stress in health and disease. Curr Opin Cell Biol. 2006;18:444-452.
133. Bertolotti A, Wang X, Novoa I, et al. Increased sensitivity to dextran sodium sulfate colitis in IRE1beta-deficient mice. J Clin Invest. 2001; 107:585-593.
134. Shkoda A, Ruiz PA, Daniel H, et al. Interleukin-10 blocked endoplasmic reticulum stress in intestinal epithelial cells: impact on chronic inflammation. Gastroenterology. 2007;132:190-207.
135. Xue X, Piao JH, Nakajima A, et al. Tumor necrosis factor alpha (TNFalpha) induces the unfolded protein response (UPR) in a reactive oxygen species (ROS)-dependent fashion, and the UPR counteracts ROS accumulation by TNFalpha. J Biol Chem. 2005;280:33917-33925.
136. Pahl HL, Baeuerle PA. A novel signal transduction pathway from the endoplasmic reticulum to the nucleus is mediated by transcription factor NF-kappa B. EMBO J. 1995;14:2580-2588.
137. Hendershot LM, Wei JY, Gaut JR, et al. In vivo expression of mammalian BiP ATPase mutants causes disruption of the endoplasmic reticulum. Mol Biol Cell. 1995;6:283-296.
138. Rao RV, Peel A, Logvinova A, et al. Coupling endoplasmic reticulum stress to the cell death program: role of the ER chaperone GRP78. FEBS Lett. 2002;514:122-128.
139. Alexander WS, Hilton DJ. The role of suppressors of cytokine signaling (SOCS) proteins in regulation of the immune response. Annu Rev Immunol. 2004;22:503-529.
140. Moore KW, de Waal Malefyt R, Coffman RL, et al. Interleukin-10 and the interleukin-10 receptor. Annu Rev Immunol. 2001;19:683-765.
141. Ricchetti GA, Williams LM, Foxwell BM. Heme oxygenase 1 expression induced by IL-10 requires STAT-3 and phosphoinositol-3 kinase and is inhibited by lipopolysaccharide. J Leukoc Biol. 2004;76:719-726.
142. Roediger WE. The colonic epithelium in ulcerative colitis: an energy-deficiency disease? Lancet. 1980;2:712-715.
143. Fukushima K, Fiocchi C. Paradoxical decrease of mitochondrial DNA deletions in epithelial cells of active ulcerative colitis patients. Am J Physiol Gastrointest Liver Physiol. 2004;286:G804-813.
144. Hatoum OA, Binion DG, Otterson MF, et al. Acquired microvascular dysfunction in inflammatory bowel disease: loss of nitric oxide-mediated vasodilation. Gastroenterology. 2003;125:58-69.
145. Synnestvedt K, Furuta GT, Comerford KM, et al. Ecto-5′-nucleotidase (CD73) regulation by hypoxia-inducible factor-1 mediates permeability changes in intestinal epithelia. J Clin Invest. 2002;110:993-1002.
146. Koumenis C, Naczki C, Koritzinsky M, et al. Regulation of protein synthesis by hypoxia via activation of the endoplasmic reticulum kinase PERK and phosphorylation of the translation initiation factor eIF2alpha. Mol Cell Biol. 2002;22:7405-7416.
147. Blais JD, Filipenko V, Bi M, et al. Activating transcription factor 4 is translationally regulated by hypoxic stress. Mol Cell Biol. 2004;24: 7469-7482.
148. Comerford KM, Wallace TJ, Karhausen J, et al. Hypoxia-inducible factor-1-dependent regulation of the multidrug resistance (MDR1) gene. Cancer Res. 2002;62:3387-3394.
149. Furuta GT, Turner JR, Taylor CT, et al. Hypoxia-inducible factor 1-dependent induction of intestinal trefoil factor protects barrier function during hypoxia. J Exp Med. 2001;193:1027-1034.
150. Karhausen J, Furuta GT, Tomaszewski JE, et al. Epithelial hypoxia-inducible factor-1 is protective in murine experimental colitis. J Clin Invest. 2004;114:1098-1106.
151. Lee AS. The ER chaperone and signaling regulator GRP78/BiP as a monitor of endoplasmic reticulum stress. Methods. 2005;35:373-381.
152. Braakman I, Helenius J, Helenius A. Role of ATP and disulphide bonds during protein folding in the endoplasmic reticulum. Nature. 1992;356: 260-262.
153. Haller D. Intestinal epithelial cell signalling and host-derived negative regulators under chronic inflammation: to be or not to be activated determines the balance towards commensal bacteria. Neurogastroenterol Motil. 2006;18:184-199.
154. Shkoda A, Werner T, Daniel H, et al. Differential protein expression profile in the intestinal epithelium of patients with inflammatory bowel disease. J Proteom Res. 2007;6:1114-11125.
155. Werner T, Haller D. Intestinal epithelial cell signalling and chronic inflammation: from the proteome to specific molecular mechanisms. Mutat Res. 2007 (in press).