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Langenbeck's Archives of Surgery

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01.01.2012 | Review Article

Ulcerative colitis: immune function, tissue fibrosis and current therapeutic considerations

verfasst von: Jochen Maul, Martin Zeitz

Erschienen in: Langenbeck's Archives of Surgery | Ausgabe 1/2012

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Abstract

Background

Ulcerative colitis (UC) is a complex disease in which the interaction of genetic, environmental and microbial factors drives chronic intestinal inflammation that finally leads to extensive tissue fibrosis.

Discussion

The present review discusses the current knowledge on genetic susceptibility, especially of the IL-12/IL-23 pathway, the pathophysiologic role of the involved cytokines (e.g. IL-13, IL-23, TGFβ1) and immune cells (e.g. T cells, epithelial cells, fibroblasts) in UC followed by an overview on actual therapeutic considerations. These future therapies will target selectively the involved cell types by blocking their activation and its downstream signalling, by inhibiting their migration to the inflamed site and by anti-cytokine strategies. This may avoid–when initiated in time–the perpetuation of the inflammatory mechanisms thus preventing fibrosis. With respect to animal models that have guided the most productive efforts for understanding human inflammatory bowel disease, these will be shortly discussed in the respective context.

Loftus EV Jr (2004) Clinical epidemiology of inflammatory bowel disease: incidence, prevalence, and environmental influences. Gastroenterology 126:1504–1517PubMedCrossRef

Maul J, Duchmann R (2008) Can loss of immune tolerance cause IBD? Inflamm Bowel Dis 14:S115–S116PubMedCrossRef

Ardizzone S, Puttini PS, Cassinotti A, Porro GB (2008) Extraintestinal manifestations of inflammatory bowel disease. Dig Liver Dis 40:S253–S259PubMedCrossRef

Duchmann R, Maul J, Heller F, Zeitz M (2003) Basic mechanisms of inflammation in ulcerative colitis. Dig Surg 20:347–349

Fichtner-Feigl S, Strober W, Geissler EK, Schlitt H (2008) Cytokines mediating the induction of chronic colitis and colitis-associated fibrosis. Mucosal Immunol 1:S24–S27PubMedCrossRef

Cho JH (2008) The genetics and immunopathogenesis of inflammatory bowel disease. Nat Rev Immunol 8:458–466PubMedCrossRef

Strober W, Fuss IJ, Blumberg RS (2002) The immunology of mucosal models of inflammation. Annu Rev Immunol 20:495–549PubMedCrossRef

Caprilli R, Lapaquette P, Darfeuille-Michaud A (2010) Eating the enemy in Crohn's disease: an old theory revisited. J Crohn Colitis 4:377–383CrossRef

Cargill M, Schrodi SJ, Chang M, Garcia VE, Brandon R, Callis KP, Matsunami N, Ardlie KG, Civello D, Catanese JJ, Leong DU, Panko JM, McAllister LB, Hansen CB, Papenfuss J, Prescott SM, White TJ, Leppert MF, Krueger GG, Begovich AB (2007) A large-scale genetic association study confirms IL12B and leads to the identification of IL23R as psoriasis-risk genes. Am J Hum Genet 80:273–290PubMedCrossRef

10.

Burtton P, Clayton D, Cardon L (2007) Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants. Nat Genet 39:1329–1337CrossRef

11.

Yu W, Lin Z, Pastor DM, Hegarty JP, Chen X, Kelly AA, Wang Y, Poritz LS, Koltun WA (2010) Genes regulated by Nkx2-3 in sporadic and inflammatory bowel disease-associated colorectal cancer cell lines. Dig Dis Sci 55:3171–3180PubMedCrossRef

12.

Goyette P, Lefebvre C, Ng A, Brant SR, Cho JH, Duerr RH, Silverberg MS, Taylor KD, Latiano A, Aumais G, Deslandres C, Jobin G, Annese V, Daly MJ, Xavier RJ, Rioux JD (2008) Gene-centric association mapping of chromosome 3p implicates MST1 in IBD pathogenesis. Mucosal Immunol 1:131–138PubMedCrossRef

13.

Long SA, Cerosaletti K, Wan JY, Ho J, Tatum M, Wei S, Shilling HG, Buckner JH (2011) An autoimmune-associated variant in PTPN2 reveals an impairment of IL-2R signaling in CD4+ T cells. Genes Immun 12:116–125PubMedCrossRef

14.

Bekker-Jensen S, Danielsen JR, Fugger K, Gromova I, Nerstedt A, Lukas C, Bartek J, Lukas J, Mailand N (2010) HERC2 coordinates ubiquitin-dependent assembly of DNA repair factors on damaged chromosomes. Nat Cell Biol 12:80–86PubMedCrossRef

15.

Chan I, Liu L, Hamada T, Sethuraman G, McGrath JA (2007) The molecular basis of lipoid proteinosis: mutations in extracellular matrix protein 1. Exp Dermatol 16:881–890PubMedCrossRef

16.

Matsuda A, Suzuki Y, Honda G, Muramatsu S, Matsuzaki O, Nagano Y, Doi T, Shimotohno K, Harada T, Nishida E, Hayashi H, Sugano S (2003) Large-scale identification and characterization of human genes that activate NF-[kappa]B and MAPK signaling pathways. Oncogene 22:3307–3318PubMedCrossRef

17.

Franke A, Balschun T, Karlsen TH, Hedderich J, May S, Lu T, Schuldt D, Nikolaus S, Rosenstiel P, Krawczak M, Schreiber S (2008) Replication of signals from recent studies of Crohn's disease identifies previously unknown disease loci for ulcerative colitis. Nat Genet 40:713–715PubMedCrossRef

18.

Fisher SA, Tremelling M, Anderson CA, Gwilliam R, Bumpstead S, Prescott NJ, Nimmo ER, Massey D, Berzuini C, Johnson C, Barrett JC, Cummings FR, Drummond H, Lees CW, Onnie CM, Hanson CE, Blaszczyk K, Inouye M, Ewels P, Ravindrarajah R, Keniry A, Hunt S, Carter M, Watkins N, Ouwehand W, Lewis CM, Cardon L, Lobo A, Forbes A, Sanderson J, Jewell DP, Mansfield JC, Deloukas P, Mathew CG, Parkes M, Satsangi J (2008) Genetic determinants of ulcerative colitis include the ECM1 locus and five loci implicated in Crohn's disease. Nat Genet 40:710–712PubMedCrossRef

19.

Brand S (2009) Crohn's disease: Th1, Th17 or both? The change of a paradigm: new immunological and genetic insights implicate Th17 cells in the pathogenesis of Crohn's disease. Gut 58:1152–1167PubMedCrossRef

20.

Deusch K, Mauthe B, Reiter C, Riethmüller G, Classen M (1993) CD4-antibody treatment of inflammatory bowel disease: one year follow-up. Gastroenterology 104:A691

21.

Emmrich J, Seyfarth M, Fleig WE, Emmrich F (1991) Treatment of inflammatory bowel disease with anti-CD4 monoclonal antibody. Lancet 338:570–571PubMedCrossRef

22.

Kozuch PL, Hanauer SB (2006) General principles and pharmacology of biologics in inflammatory bowel disease. Gastroenterol Clin North Am 35:757–773PubMedCrossRef

23.

Plevy S, Salzberg B, Van Assche G, Regueiro M, Hommes D, Sandborn W, Hanauer S, Targan S, Mayer L, Mahadevan U, Frankel M, Lowder J (2007) A phase I study of visilizumab, a humanized anti-CD3 monoclonal antibody, in severe steroid-refractory ulcerative colitis. Gastroenterology 133:1414–1422PubMedCrossRef

24.

Baumgart DC, Targan SR, Dignass AU, Mayer L, Assche GV, Hommes DW, Hanauer SB, Mahadevan U, Reinisch W, Plevy SE, Salzberg BA, Buchman AL, Mechkov GM, Krastev ZA, Lowder JN, Frankel MB, Sandborn WJ (2010) Prospective randomized open-label multicenter phase I/II dose escalation trial of visilizumab (HuM291) in severe steroid-refractory ulcerative colitis. Inflamm Bowel Dis 16:620–629PubMed

25.

Sandborn W, Colombel J, Frankel MB, Hommes D, Lowder J, Mayer L, Plevy SE, Stokkers P, Travis S, Van Assche GA, Targan S (2009) A placebo-controlled trial of visilizumab in patients with intravenous (IV) steroid refractory ulcerative colitis (UC). Gastroenterology 136:A64

26.

Sandborn WJ, Hanauer SB, Katz S, Safdi M, Wolf DG, Baerg RD, Tremaine WJ, Johnson T, Diehl NN, Zinsmeister AR (2001) Etanercept for active Crohn's disease: a randomized, double-blind, placebo-controlled trial. Gastroenterology 121:1088–1094PubMedCrossRef

27.

Rutgeerts P, Lemmens L, Van Assche G, Noman M, Borghini-Fuhrer I, Goedkoop R (2003) Treatment of active Crohn's disease with onercept (recombinant human soluble p55 tumour necrosis factor receptor): results of a randomized, open-label, pilot study. Aliment Pharmacol Ther 17:185–192PubMedCrossRef

28.

Travis S, Yap LM, Hawkey C, Warren B, Lazarov M, Fong T, Tesi RJ (2005) RDP58 is a novel and potentially effective oral therapy for ulcerative colitis. Inflamm Bowel Dis 11:713–719PubMedCrossRef

29.

Lofberg R, Neurath M, Ost A, Pettersson S (2002) Topical NFkB antisense oligonucleotides in patients with active distal colonic IBD. A randomised controlled pilot trial. Gastroenterology 122:A60CrossRef

30.

Danese S, Angelucci E, Malesci A, Caprilli R (2008) Biological agents for ulcerative colitis: hypes and hopes. Med Res Rev 28:201–218PubMedCrossRef

31.

Van Assche G, Sandborn WJ, Feagan BG, Salzberg BA, Silvers D, Monroe PS, Pandak WM, Anderson FH, Valentine JF, Wild GE, Geenen DJ, Sprague R, Targan SR, Rutgeerts P, Vexler V, Young D, Shames RS (2006) Daclizumab, a humanised monoclonal antibody to the interleukin 2 receptor (CD25), for the treatment of moderately to severely active ulcerative colitis: a randomised, double blind, placebo controlled, dose ranging trial. Gut 55:1568–1574PubMedCrossRef

32.

Creed TJ, Probert CSJ, Norman MN, Moorghen M, Shepherd NA, Hearing SD, Dayan CM, THE BASBUC INVESTIGATORS1 (2006) Basiliximab for the treatment of steroid-resistant ulcerative colitis: further experience in moderate and severe disease. Aliment Pharmacol Ther 23:1435–1442PubMedCrossRef

33.

Ghosh S, Goldin E, Gordon FH, Malchow HA, Rask-Madsen J, Rutgeerts P, Vyhnálek P, Zádorová Z, Palmer T, Donoghue S (2003) Natalizumab for active Crohn's disease. N Engl J Med 348:24–32PubMedCrossRef

34.

Gordon FH, Hamilton MI, Donoghue S, Greenlees C, Palmer T, Rowley-Jones D, Dhillon AP, Amlot PL, Pounder RE (2002) A pilot study of treatment of active ulcerative colitis with natalizumab, a humanized monoclonal antibody to alpha-4 integrin. Aliment Pharmacol Ther 16:699–705PubMedCrossRef

35.

Feagan BG, Greenberg GR, Wild G, Fedorak RN, Paré P, McDonald JWD, Dubé R, Cohen A, Steinhart AH, Landau S, Aguzzi RA, Fox IH, Vandervoort MK (2005) Treatment of ulcerative colitis with a humanized antibody to the alpha4beta7 integrin. N Engl J Med 352:2499–2507PubMedCrossRef

36.

Van Deventer SJH, Wedel MK, Baker BF, Xia S, Chuang E, Miner PB (2006) A phase II dose ranging, double-blind, placebo-controlled study of alicaforsen enema in subjects with acute exacerbation of mild to moderate left-sided ulcerative colitis. Aliment Pharmacol Ther 23:1415–1425PubMedCrossRef

37.

Suzuki K, Kawauchi Y, Palaniyandi SS, Veeraveedu PT, Fujii M, Yamagiwa S, Yoneyama H, Han GD, Kawachi H, Okada Y, Ajioka Y, Watanabe K, Hosono M, Asakura H, Aoyagi Y, Narumi S (2007) Blockade of interferon-gamma-inducible protein-10 attenuates chronic experimental colitis by blocking cellular trafficking and protecting intestinal epithelial cells. Pathol Int 57:413–420PubMedCrossRef

38.

Bendelac A, Savage PB, Teyton L (2007) The biology of NKT cells. Annu Rev Immunol 25:297–336PubMedCrossRef

39.

Brigl M, Brenner MB (2004) CD1: antigen presentation and T cell function. Annu Rev Immunol 22:817–890PubMedCrossRef

40.

Fuss IJ, Heller F, Boirivant M, Leon F, Yoshida M, Fichtner-Feigl S, Yang Z, Exley M, Kitani A, Blumberg RS, Mannon P, Strober W (2004) Nonclassical CD1d-restricted NK T cells that produce IL-13 characterize an atypical Th2 response in ulcerative colitis. J Clin Invest 113:1490–1497PubMed

41.

van Dieren JM, van der Woude CJ, Kuipers EJ, Escher JC, Samsom JN, Blumberg RS, Nieuwenhuis EES (2007) Roles of CD1d-restricted NKT cells in the intestine. Inflamm Bowel Dis 13:1146–1152PubMedCrossRef

42.

Omata F, Birkenbach M, Matsuzaki S, Christ AD, Blumberg RS (2001) The expression of IL-12 p40 and its homologue, Epstein-Barr virus-induced gene 3, in inflammatory bowel disease. Inflamm Bowel Dis 7:215–220PubMedCrossRef

43.

Heller F, Fuss IJ, Nieuwenhuis EE, Blumberg RS, Strober W (2002) Oxazolone colitis, a Th2 colitis model resembling ulcerative colitis, is mediated by IL-13-producing NK-T cells. Immunity 17:629–638PubMedCrossRef

44.

Gauvreau GM, Boulet L, Cockcroft DW, FitzGerald JM, Carlsten C, Davis BE, Deschesnes F, Duong M, Durn BL, Howie KJ, Hui L, Kasaian MT, Killian KJ, Strinich TX, Watson RM, Y N, Zhou S, Raible D, O'Byrne PM (2011) The effects of IL-13 blockade on allergen-induced airway responses in mild atopic asthma. Am J Respir Crit Care Med (in press)

45.

Baecher-Allan C, Brown JA, Freeman GJ, Hafler DA (2001) CD4+CD25 high regulatory cells in human peripheral blood. J Immunol 167:1245–1253PubMed

46.

Dieckmann D, Plottner H, Berchtold S, Berger T, Schuler G (2001) Ex vivo isolation and characterization of CD4(+)CD25(+) T cells with regulatory properties from human blood. J Exp Med 193:1303–1310PubMedCrossRef

47.

Jonuleit H, Schmitt E, Stassen M, Tuettenberg A, Knop J, Enk AH (2001) Identification and functional characterization of human CD4(+)CD25(+) T cells with regulatory properties isolated from peripheral blood. J Exp Med 193:1285–1294PubMedCrossRef

48.

Maul J, Loddenkemper C, Mundt P, Berg E, Giese T, Stallmach A, Zeitz M, Duchmann R (2005) Peripheral and intestinal regulatory CD4+ CD25(high) T cells in inflammatory bowel disease. Gastroenterology 128:1868–1878PubMedCrossRef

49.

Epple H, Loddenkemper C, Kunkel D, Tröger H, Maul J, Moos V, Berg E, Ullrich R, Schulzke J, Stein H, Duchmann R, Zeitz M, Schneider T (2006) Mucosal but not peripheral FOXP3+ regulatory T cells are highly increased in untreated HIV infection and normalize after suppressive HAART. Blood 108:3072–3078PubMedCrossRef

50.

Yu QT, Saruta M, Avanesyan A, Fleshner PR, Banham AH, Papadakis KA (2007) Expression and functional characterization of FOXP3+ CD4+ regulatory T cells in ulcerative colitis. Inflamm Bowel Dis 13:191–199PubMedCrossRef

51.

Makita S, Kanai T, Oshima S, Uraushihara K, Totsuka T, Sawada T, Nakamura T, Koganei K, Fukushima T, Watanabe M (2004) CD4+CD25bright T cells in human intestinal lamina propria as regulatory cells. J Immunol 173:3119–3130PubMed

52.

Rieger K, Loddenkemper C, Maul J, Fietz T, Wolff D, Terpe H, Steiner B, Berg E, Miehlke S, Bornhäuser M, Schneider T, Zeitz M, Stein H, Thiel E, Duchmann R, Uharek L (2006) Mucosal FOXP3+ regulatory T cells are numerically deficient in acute and chronic GvHD. Blood 107:1717–1723PubMedCrossRef

53.

Zhang X, Izikson L, Liu L, Weiner HL (2001) Activation of CD25(+)CD4(+) regulatory T cells by oral antigen administration. J Immunol 167:4245–4253PubMed

54.

Gad M, Brimnes J, Claesson MH (2003) CD4+ T regulatory cells from the colonic lamina propria of normal mice inhibit proliferation of enterobacteria-reactive, disease-inducing Th1-cells from scid mice with colitis. Clin Exp Immunol 131:34–40PubMedCrossRef

55.

Read S, Malmström V, Powrie F (2000) Cytotoxic T lymphocyte-associated antigen 4 plays an essential role in the function of CD25(+)CD4(+) regulatory cells that control intestinal inflammation. J Exp Med 192:295–302PubMedCrossRef

56.

Mottet C, Uhlig HH, Powrie F (2003) Cutting edge: cure of colitis by CD4+CD25+ regulatory T cells. J Immunol 170:3939–3943PubMed

57.

Hori S, Nomura T, Sakaguchi S (2003) Control of regulatory T cell development by the transcription factor Foxp3. Science 299:1057–1061PubMedCrossRef

58.

Bluestone JA, Abbas AK (2003) Natural versus adaptive regulatory T cells. Nat Rev Immunol 3:253–257PubMedCrossRef

59.

Hori S (2010) Developmental plasticity of Foxp3+ regulatory T cells. Curr Opin Immunol 22:575–582PubMedCrossRef

60.

Saruta M, Yu QT, Fleshner PR, Mantel P, Schmidt-Weber CB, Banham AH, Papadakis KA (2007) Characterization of FOXP3+CD4+ regulatory T cells in Crohn's disease. Clin Immunol 125:281–290PubMedCrossRef

61.

Takahashi M, Nakamura K, Honda K, Kitamura Y, Mizutani T, Araki Y, Kabemura T, Chijiiwa Y, Harada N, Nawata H (2006) An inverse correlation of human peripheral blood regulatory T cell frequency with the disease activity of ulcerative colitis. Dig Dis Sci 51:677–686PubMedCrossRef

62.

Holmén N, Lundgren A, Lundin S, Bergin A, Rudin A, Sjövall H, Ohman L (2006) Functional CD4+CD25high regulatory T cells are enriched in the colonic mucosa of patients with active ulcerative colitis and increase with disease activity. Inflamm Bowel Dis 12:447–456PubMedCrossRef

63.

Sumida Y, Nakamura K, Kanayama K, Akiho H, Teshima T, Takayanagi R (2008) Preparation of functionally preserved CD4+ CD25high regulatory T cells from leukapheresis products from ulcerative colitis patients, applicable to regulatory T-cell transfer therapy. Cytotherapy 10:698–710PubMedCrossRef

64.

Buruiana FE, Solà I, Alonso-Coello P (2010) Recombinant human interleukin 10 for induction of remission in Crohn's disease. In: Alonso-Coello P (ed) Cochrane Database of Systematic Reviews, The Cochrane Collaboration. Wiley, Chichester, UK

65.

Schreiber S, Fedorak RN, Wild G, Gangl A, Targan SR, Jacyna M, Wright JP, Kilian A, Cohard M, LeBeaut A, Tremaine W (1998) Ulcerative Colitis IL-10 Cooperative Study Group. Safety and tolerance of rHuIL-10 treatment in patients with mild/moderate active ulcerative colitis. Gastroenterology 114:A1080–A1081

66.

Steidler L, Rottiers P, Coulie B (2009) Actobiotics™ as a novel method for cytokine delivery. Ann N Y Acad Sci 1182:135–145PubMedCrossRef

67.

Gregori S, Roncarolo MG, Bacchetta R (2011) Methods for in vitro generation of human type 1 regulatory T cells. Methods Mol Biol 677:31–46PubMedCrossRef

68.

Desreumaux P, Beaugerie L, Bouhnik Y, Nachury M, Hebuterne X, Foussat A, Clerget-Chossat N, Forte M, Lemann M (2010) Crohn's disease and autologous type 1 regulatory T (Tr1) lmyphocytes (CATS1) cellular therapy open label phase I study. Gut 59:A73

69.

Iwakura Y, Ishigame H (2006) The IL-23/IL-17 axis in inflammation. J Clin Invest 116:1218–1222PubMedCrossRef

70.

Wiekowski MT, Leach MW, Evans EW, Sullivan L, Chen S, Vassileva G, Bazan JF, Gorman DM, Kastelein RA, Narula S, Lira SA (2001) Ubiquitous transgenic expression of the IL-23 subunit p19 induces multiorgan inflammation, runting, infertility, and premature death. J Immunol 166:7563–7570PubMed

71.

Becker C, Dornhoff H, Neufert C, Fantini MC, Wirtz S, Huebner S, Nikolaev A, Lehr H, Murphy AJ, Valenzuela DM, Yancopoulos GD, Galle PR, Karow M, Neurath MF (2006) Cutting edge: IL-23 cross-regulates IL-12 production in T cell-dependent experimental colitis. J Immunol 177:2760–2764PubMed

72.

Pickert G, Neufert C, Leppkes M, Zheng Y, Wittkopf N, Warntjen M, Lehr H, Hirth S, Weigmann B, Wirtz S, Ouyang W, Neurath MF, Becker C (2009) STAT3 links IL-22 signaling in intestinal epithelial cells to mucosal wound healing. J Exp Med 206:1465–1472PubMedCrossRef

73.

Sandborn WJ, Feagan BG, Fedorak RN, Scherl E, Fleisher MR, Katz S, Johanns J, Blank M, Rutgeerts P (2008) A randomized trial of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with moderate-to-severe Crohn's disease. Gastroenterology 135:1130–1141PubMedCrossRef

74.

West K (2009) CP-690550, a JAK3 inhibitor as an immunosuppressant for the treatment of rheumatoid arthritis, transplant rejection, psoriasis and other immune-mediated disorders. Curr Opin Investig Drugs 10:491–504PubMed

75.

Debril M, Renaud J, Fajas L, Auwerx J (2001) The pleiotropic functions of peroxisome proliferator-activated receptor gamma. J Mol Med 79:30–47PubMedCrossRef

76.

Kliewer SA, Umesono K, Noonan DJ, Heyman RA, Evans RM (1992) Convergence of 9-cis retinoic acid and peroxisome proliferator signalling pathways through heterodimer formation of their receptors. Nature 358:771–774PubMedCrossRef

77.

Jackson SM, Parhami F, Xi X, Berliner JA, Hsueh WA, Law RE, Demer LL (1999) Peroxisome proliferator-activated receptor activators target human endothelial cells to inhibit leukocyte-endothelial cell interaction. Arterioscler Thromb Vasc Biol 19:2094–2104PubMedCrossRef

78.

Yang XY, Wang LH, Chen T, Hodge DR, Resau JH, DaSilva L, Farrar WL (2000) Activation of human T lymphocytes is inhibited by peroxisome proliferator-activated receptor γ (PPARγ) agonists. J Biol Chem 275:4541–4544PubMedCrossRef

79.

Dubuquoy L, Rousseaux C, Thuru X, Peyrin-Biroulet L, Romano O, Chavatte P, Chamaillard M, Desreumaux P (2006) PPARγ as a new therapeutic target in inflammatory bowel diseases. Gut 55:1341–1349PubMedCrossRef

80.

Lefebvre M, Paulweber B, Fajas L, Woods J, McCrary C, Colombel J, Najib J, Fruchart J, Datz C, Vidal H, Desreumaux P, Auwerx J (1999) Peroxisome proliferator-activated receptor gamma is induced during differentiation of colon epithelium cells. J Endocrinol 162:331–340PubMedCrossRef

81.

Dubuquoy L, Jansson EÅ, Deeb S, Rakotobe S, Karoui M, Colombel J, Auwerx J, Pettersson S, Desreumaux P (2003) Impaired expression of peroxisome proliferator-activated receptor [gamma] in ulcerative colitis. Gastroenterology 124:1265–1276PubMedCrossRef

82.

Saubermann LJ, Nakajima A, Wada K, Zhao S, Terauchi Y, Kadowaki T, Aburatani H, Matsuhashi N, Nagai R, Blumberg RS (2002) Peroxisome proliferator-activated receptor gamma agonist ligands stimulate a Th2 cytokine response and prevent acute colitis. Inflamm Bowel Dis 8:330–339PubMedCrossRef

83.

Su CG, Wen X, Bailey ST, Jiang W, Rangwala SM, Keilbaugh SA, Flanigan A, Murthy S, Lazar MA, Wu GD (1999) A novel therapy for colitis utilizing PPAR-γ ligands to inhibit the epithelial inflammatory response. J Clin Invest 104:383–389PubMedCrossRef

84.

Takagi T, Naito Y, Tomatsuri N, Handa O, Ichikawa H, Yoshida N, Yoshikawa T (2002) Pioglitazone, a PPAR-gamma ligand, provides protection from dextran sulfate sodium-induced colitis in mice in association with inhibition of the NF-kappaB-cytokine cascade. Redox Rep 7:283–289PubMedCrossRef

85.

Lewis JD, Lichtenstein GR, Deren JJ, Sands BE, Hanauer SB, Katz JA, Lashner B, Present DH, Chuai S, Ellenberg JH, Nessel L, Wu GD (2008) Rosiglitazone for active ulcerative colitis. Gastroenterology 134:688–695PubMedCrossRef

86.

Nissen SE, Wolski K (2010) Rosiglitazone revisited: an updated meta-analysis of risk for myocardial infarction and cardiovascular mortality. Arch Intern Med 170:1191–1201PubMedCrossRef

87.

Graham DJ, Ouellet-Hellstrom R, MaCurdy TE, Ali F, Sholley C, Worrall C, Kelman JA (2010) Risk of acute myocardial infarction, stroke, heart failure, and death in elderly Medicare patients treated with rosiglitazone or pioglitazone. JAMA 304:411–418PubMedCrossRef

88.

Rousseaux C, Lefebvre B, Dubuquoy L, Lefebvre P, Romano O, Auwerx J, Metzger D, Wahli W, Desvergne B, Naccari GC, Chavatte P, Farce A, Bulois P, Cortot A, Colombel JF, Desreumaux P (2005) Intestinal antiinflammatory effect of 5-aminosalicylic acid is dependent on peroxisome proliferator–activated receptor-γ. J Exp Med 201:1205–1215PubMedCrossRef

89.

Seibold F, Brandwein S, Simpson S, Terhorst C, Elson CO (1998) pANCA represents a cross-reactivity to enteric bacterial antigens. J Clin Immunol 18:153–160PubMedCrossRef

90.

Shih DQ, Targan SR (2008) Immunopathogenesis of inflammatory bowel disease. World J Gastroenterol 14:390–400PubMedCrossRef

91.

Targan SR, Karp LC (2005) Defects in mucosal immunity leading to ulcerative colitis. Immunol Rev 206:296–305PubMedCrossRef

92.

Mizoguchi E, Mizoguchi A, Chiba C, Niles JL, Bhan AK (1997) Antineutrophil cytoplasmic antibodies in T-cell receptor alpha-deficient mice with chronic colitis. Gastroenterology 113:1828–1835PubMedCrossRef

93.

Mizoguchi A, Mizoguchi E, Chiba C, Bhan AK (1996) Role of appendix in the development of inflammatory bowel disease in TCR-alpha mutant mice. J Exp Med 184:707–715PubMedCrossRef

94.

Rieder F, Fiocchi C (2009) Intestinal fibrosis in IBD - a dynamic, multifactorial process. Nat Rev Gastroenterol Hepatol 6:228–235PubMedCrossRef

95.

Fichtner-Feigl S, Strober W, Kawakami K, Puri RK, Kitani A (2006) IL-13 signaling through the IL-13[alpha]2 receptor is involved in induction of TGF-[beta]1 production and fibrosis. Nat Med 12:99–106PubMedCrossRef

96.

Fichtner-Feigl S, Young CA, Kitani A, Geissler EK, Schlitt H, Strober W (2008) IL-13 signaling via IL-13R[alpha]2 induces major downstream fibrogenic factors mediating fibrosis in chronic TNBS colitis. Gastroenterology 135:2003–2013.e7PubMedCrossRef

97.

Kobori A, Yagi Y, Imaeda H, Ban H, Bamba S, Tsujikawa T, Saito Y, Fujiyama Y, Andoh A (2010) Interleukin-33 expression is specifically enhanced in inflamed mucosa of ulcerative colitis. J Gastroenterol 45:999–1007PubMedCrossRef

98.

Schmitz J, Owyang A, Oldham E, Song Y, Murphy E, McClanahan TK, Zurawski G, Moshrefi M, Qin J, Li X, Gorman DM, Bazan JF, Kastelein RA (2005) IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines. Immunity 23:479–490PubMedCrossRef

99.

Rankin AL, Mumm JB, Murphy E, Turner S, Yu N, McClanahan TK, Bourne PA, Pierce RH, Kastelein R, Pflanz S (2010) IL-33 induces IL-13-dependent cutaneous fibrosis. J Immunol 184:1526–1535PubMedCrossRef

100.

Sponheim J, Pollheimer J, Olsen T, Balogh J, Hammarstrom C, Loos T, Kasprzycka M, Sorensen DR, Nilsen HR, Kuchler AM, Vatn MH, Haraldsen G (2010) Inflammatory bowel disease-associated interleukin-33 is preferentially expressed in ulceration-associated myofibroblasts. Am J Pathol 177:2804–2815PubMedCrossRef

101.

Otte J, Rosenberg IM, Podolsky DK (2003) Intestinal myofibroblasts in innate immune responses of the intestine. Gastroenterology 124:1866–1878PubMedCrossRef

102.

Fedorak RN, Gangl A, Elson CO, Rutgeerts P, Schreiber S, Wild G, Hanauer SB, Kilian A, Cohard M, LeBeaut A, Feagan B (2000) Recombinant human interleukin 10 in the treatment of patients with mild to moderately active Crohn's disease. The Interleukin 10 Inflammatory Bowel Disease Cooperative Study Group. Gastroenterology 119:1473–1482PubMedCrossRef

103.

Sinha A, Nightingale J, West KP, Berlanga-Acosta J, Playford RJ (2003) Epidermal growth factor enemas with oral mesalamine for mild-to-moderate left-sided ulcerative colitis or proctitis. N Engl J Med 349:350–357PubMedCrossRef

Titel: Ulcerative colitis: immune function, tissue fibrosis and current therapeutic considerations
verfasst von: Jochen Maul
Martin Zeitz
Publikationsdatum: 01.01.2012
Verlag: Springer-Verlag
Erschienen in: Langenbeck's Archives of Surgery / Ausgabe 1/2012
Print ISSN: 1435-2443
Elektronische ISSN: 1435-2451
DOI: https://doi.org/10.1007/s00423-011-0789-4

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Abstract

Background

Discussion

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