Abstract
Inflammatory Bowel Diseases, Crohn’s disease and ulcerative colitis, result from the uncontrolled inflammation that occurs in genetically susceptible individuals and the dysregulation of the innate and adaptive immune systems. The response of these immune systems to luminal gut microbiota and their products results in altered intestinal permeability, loss of barrier function, and mucosal inflammation and ulceration. Animal models of experiment intestinal inflammation have been developed that leverage the development of spontaneous inflammation in certain mouse strains, e.g. Samp1/Yit mice, or induction of inflammation using gene-targeting e.g. IL-10 null mice, administration of exogenous agents e.g. DSS, or adoptive transfer of T-cells into immunodeficient mice, e.g. CD4+ CD45RbHi T-cell transfer. Colitis induced by rectal instillation of the haptenizing agent, 2,4,6 trinitrobenzene sulfonic acid, is one of the most commonly used and well-characterized models of Crohn’s disease in humans.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Jostins L, Ripke S, Weersma RK, Duerr RH et al (2012) Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 491:119–124
Ott S, Musfeldt J, Wenderoth M, Hampe DFJ et al (2004) Reduction in diversity of the colonic mucosa associated bacterial microflora in patients with active inflammatory bowel disease. Gut 53:685–693
Joossens M, Huys G, Cnockaert M, De Preter V, Verbeke K, Rutgeerts P, Vandamme P, Vermeire S (2011) Dysbiosis of the faecal microbiota in patients with Crohn’s disease and their unaffected relatives. Gut 60:631–637
Andoh A, Imaeda H, Aomatsu T, Inatomi O et al (2011) Comparison of the fecal microbiota profiles between ulcerative colitis and Crohn’s disease using terminal restriction fragment length polymorphism analysis. J Gastroenterol 46:479–486
Satsangi J, Silverberg MS, Vermeire S, Colombel J-F (2006) The Montreal classification of inflammatory bowel disease: controversies, consensus, and implications. Gut 55:749–753
Blumberg RS, Saubermann LJ, Strober W (1999) Animal models of mucosal inflammation and their relation to human inflammatory bowel disease. Curr Opin Immunol 11:648–656
Neurath MF, Fuss I, Kelsall BL, Stuber E, Strober W (1995) Antibodies to interleukin 12 abrogate established experimental colitis in mice. J Exp Med 182:1281–1290
Neurath MF, Fuss I, Pasparakis M, Alexopoulou L et al (1997) Predominant pathogenic role of tumor necrosis factor in experimental colitis in mice. Eur J Immunol 27:1743–1750
Scheiffele F, Fuss IJ (2001) Induction of TNBS colitis in mice. Curr Protoc Immunol Chapter 15:Unit 15.19
Fichtner-Feigl S, Fuss IJ, Young CA, Watanabe T, Geissler EK, Schlitt HJ, Kitani A, Strober W (2007) Induction of IL-13 triggers TGF-beta1-dependent tissue fibrosis in chronic 2,4,6-trinitrobenzene sulfonic acid colitis. J Immunol 178:5859–5870
Fichtner-Feigl S, Young CA, Kitani A, Geissler EK, Schlitt H-J, Strober W (2008) IL-13 signaling via IL-13Rα2 induces major downstream fibrogenic factors mediating fibrosis in chronic TNBS colitis. Gastroenterology 135:2003–2013
Hazelgrove KB, Flynn RS, Qiao LY, Grider JR, Kuemmerle JF (2009) Endogenous IGF-I and αvβ3 integrin ligands regulate increased smooth muscle growth in TNBS-induced colitis. Am J Physiol Gastrointest Liver Physiol 296:G1230–G1237
Mahavadi S, Flynn RS, Grider JR, Qiao L-Y, Murthy KS, Hazelgrove KB, Kuemmerle JF (2011) Amelioration of excess collagen IαI, fibrosis, and smooth muscle growth in TNBS-induced colitis in IGF-I(+/−) mice. Inflamm Bowel Dis 17:711–719
Bouma G, Kaushiva A, Strober W (2002) Experimental murine colitis is regulated by two genetic loci, including one on chromosome 11 that regulates IL-12 responses. Gastroenterology 123:554–565
Li C, Flynn S, Grider JR, Murthy KS, Kellum JM, Akbari HM, Kuemmerle JF (2013) Increased activation of latent TGF-β1 by αVβ3 in human Crohn’s disease and fibrosis in TNBS colitis can be prevented by cilengitide. Inflamm Bowel Dis 19:2829–2839
Lawrance IC, Wu F, Leite AZA, Willis J, West GA, Fiocchi C, Chakravarti S (2003) A murine model of chronic inflammation-induced intestinal fibrosis down-regulated by antisense NF-κB. Gastroenterology 125:1750–1761
Rieder F, Kessler S, Sans M, Fiocchi C (2012) Animal models of intestinal fibrosis: new tools for the understanding of pathogenesis and therapy of human disease. Am J Physiol Gastrointest Liver Physiol 303:G786–G801
Li C, Kuemmerle JF (2014) Mechanisms that mediate the development of fibrosis in patients with Crohn’s disease. Inflamm Bowel Dis 20:1250–1258
Kuemmerle JF (1998) Synergistic regulation of NOS II expression by IL-1β and TNF-α in cultured rat colonic smooth muscle cells. Am J Physiol 274:G178–G185
Koscielny A, Wehner S, Engel DR, Kurts C, Kalff J (2011) Isolation of T cells and dendritic cells from peripheral intestinal tissue, Peyer’s patches and mesenteric lymph nodes in mice after intestinal manipulation. Protocol Exchange (Online).
Ortolan EVP, Spadella CT, Caramori C, Machado JLM, Gregorio EA, Rabello K (2008) Microscopic, morphometric and ultrastructural analysis of anastomotic healing in the intestine of normal and diabetic rats. Exp Clin Endocrinol Diabetes 116:198–202
Wirtz S, Neufert C, Weigmann B, Neurath MF (2007) Chemically induced mouse models of intestinal inflammation. Nat Protoc 2:541–546
te Velde AA, Verstege MI, Hommes DW (2006) Critical appraisal of the current practice in murine TNBS-induced colitis. Inflamm Bowel Dis 12:995–999
Acknowledgments
This work was sponsored by NIH DK4961 and the Harrison Family Trust.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2016 Springer Science+Business Media New York
About this protocol
Cite this protocol
Kuemmerle, J.F. (2016). Murine Trinitrobenzoic Acid-Induced Colitis as a Model of Crohn’s Disease. In: Ivanov, A. (eds) Gastrointestinal Physiology and Diseases. Methods in Molecular Biology, vol 1422. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-3603-8_22
Download citation
DOI: https://doi.org/10.1007/978-1-4939-3603-8_22
Published:
Publisher Name: Humana Press, New York, NY
Print ISBN: 978-1-4939-3601-4
Online ISBN: 978-1-4939-3603-8
eBook Packages: Springer Protocols