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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
MeSH Review


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Disease relevance of Colitis


Psychiatry related information on Colitis

  • We have previously demonstrated that trinitrobenzene sulphonic acid (TNBS)-induced colitis in guinea pig is associated with hyperexcitability of myenteric AH neurones, enhanced synaptic activity in the myenteric plexus, increased serotonin (5-HT) availability in the mucosa, and decreased propulsive motor activity [6].
  • METHODS: The effects of saline and SCFA enemas (acetate, propionate and particularly butyrate) were studied on visceral pain thresholds following colonic distension in control rats and in rats with colitis (instilled with trinitrobenzene sulfonic acid (TNBS)) [7].

High impact information on Colitis

  • Having found previously that treatment with transdermal nicotine patches and mesalamine (5-aminosalicylic acid) has a beneficial effect on active colitis, we examined the value of transdermal nicotine for the maintenance of remission [8].
  • Administering enemas containing isotonic saline, or omitting treatment for periods of two to four weeks during the regimen, by contrast, did not produce any improvement or rapid relapse of the colitis [9].
  • Acute colitis with methyldopa [10].
  • We conclude that stress reactivates experimental colitis by facilitating entry of luminal contents that activate previously sensitized CD4 cells in the colon [11].
  • Here, we show that the transcription factor NF-kappa B p65 was strongly activated in TNBS-induced colitis and in colitis of interleukin-10-deficient mice [12].

Chemical compound and disease context of Colitis

  • Local administration of p65 antisense phosphorothioate oligonucleotides abrogated clinical and histological signs of colitis and was more effective in treating TNBS-induced colitis than single or daily administration of glucocorticoids [12].
  • Mice lacking ITF had impaired mucosal healing and died from extensive colitis after oral administration of dextran sulfate sodium, an agent that causes mild epithelial injury in wild-type mice [13].
  • Mice treated with anti-mouse CEACAM1-specific monoclonal antibody (mAb) CC1 during the effector phase exhibited a reduced severity of trinitrobenzene sulfonic acid colitis in association with decreased interferon (IFN)-gamma production [14].
  • Carbon monoxide ameliorates chronic murine colitis through a heme oxygenase 1-dependent pathway [15].
  • This feature of oxazolone colitis as well as its cytokine profile have important implications to the pathogenesis and treatment of UC [16].
  • Larger increases in tissue substance P were seen in acute than in chronic DSS, whereas CD4 T cells, beta-endorphin and MOR expression were evident only in chronic colitis [17].
  • In contrast to the beneficial effect of fenofibrate, the PPARdelta ligand GW0742 accelerated the onset of colitis in IL-10(-/-) mice [18].

Biological context of Colitis


Anatomical context of Colitis


Gene context of Colitis

  • Our aim was to identify which cell type(s) can mediate colitis in IL-10-/- mice [28].
  • The colitis appeared to be due to a dysregulated Th1 response as anti-IFN-gamma, but not anti-IL-4, prevented it [29].
  • These results demonstrate the importance of TNF production by non-T cells of the colonic mucosa in the pathogenesis of colitis and provide direct evidence for a nonredundant role of TNF-alpha in this mouse model of colitis [30].
  • These data suggest that hyperactivation of STAT3 results in severe colitis and that CIS3 plays a negative regulatory role in intestinal inflammation by downregulating STAT3 activity [31].
  • The prostaglandin receptor EP4 suppresses colitis, mucosal damage and CD4 cell activation in the gut [32].
  • Confocal microscopy analysis revealed EGFP-positive enterocytes during the early phase of bacterial colonization (1 wk) in both IL-10wt/wt and IL-10-/- mice, while the signal shifted toward lamina propria T cells, dendritic cells, neutrophils, and macrophages in IL-10-/- mice during colitis (7 wk) [33].
  • Mice deficient in both WASP and IL-4 showed no difference in histologic colitis scores at 24 weeks of age compared with WASP-deficient mice [34].
  • Collectively, systemic, but not intestinal, IL-7 is essential for the persistence of colitis, suggesting that therapeutic approaches targeting the systemic IL-7/IL-7R signaling pathway may be feasible in the treatment of inflammatory bowel diseases [35].

Analytical, diagnostic and therapeutic context of Colitis


  1. Letter: Clindamycin-associated colitis with toxic megacolon. Axelrod, M., Allon, O., Felton, M., Goldfinger, M. JAMA (1975) [Pubmed]
  2. The transcription factor T-bet regulates mucosal T cell activation in experimental colitis and Crohn's disease. Neurath, M.F., Weigmann, B., Finotto, S., Glickman, J., Nieuwenhuis, E., Iijima, H., Mizoguchi, A., Mizoguchi, E., Mudter, J., Galle, P.R., Bhan, A., Autschbach, F., Sullivan, B.M., Szabo, S.J., Glimcher, L.H., Blumberg, R.S. J. Exp. Med. (2002) [Pubmed]
  3. T helper 1 and T helper 2 cells are pathogenic in an antigen-specific model of colitis. Iqbal, N., Oliver, J.R., Wagner, F.H., Lazenby, A.S., Elson, C.O., Weaver, C.T. J. Exp. Med. (2002) [Pubmed]
  4. Composition of human colonic mucin. Selective alteration in inflammatory bowel disease. Podolsky, D.K., Isselbacher, K.J. J. Clin. Invest. (1983) [Pubmed]
  5. Neurokinin-1 (NK-1) receptor is required in Clostridium difficile- induced enteritis. Castagliuolo, I., Riegler, M., Pasha, A., Nikulasson, S., Lu, B., Gerard, C., Gerard, N.P., Pothoulakis, C. J. Clin. Invest. (1998) [Pubmed]
  6. Cyclooxygenase-2 contributes to dysmotility and enhanced excitability of myenteric AH neurones in the inflamed guinea pig distal colon. Linden, D.R., Sharkey, K.A., Ho, W., Mawe, G.M. J. Physiol. (Lond.) (2004) [Pubmed]
  7. Short-chain fatty acid enemas fail to decrease colonic hypersensitivity and inflammation in TNBS-induced colonic inflammation in rats. Tarrerias, A.L., Millecamps, M., Alloui, A., Beaughard, C., Kemeny, J.L., Bourdu, S., Bommelaer, G., Eschalier, A., Dapoigny, M., Ardid, D. Pain (2002) [Pubmed]
  8. Transdermal nicotine as maintenance therapy for ulcerative colitis. Thomas, G.A., Rhodes, J., Mani, V., Williams, G.T., Newcombe, R.G., Russell, M.A., Feyerabend, C. N. Engl. J. Med. (1995) [Pubmed]
  9. Treatment of diversion colitis with short-chain-fatty acid irrigation. Harig, J.M., Soergel, K.H., Komorowski, R.A., Wood, C.M. N. Engl. J. Med. (1989) [Pubmed]
  10. Acute colitis with methyldopa. Graham, C.F., Gallagher, K., Jones, J.K. N. Engl. J. Med. (1981) [Pubmed]
  11. The role of CD4+ lymphocytes in the susceptibility of mice to stress-induced reactivation of experimental colitis. Qiu, B.S., Vallance, B.A., Blennerhassett, P.A., Collins, S.M. Nat. Med. (1999) [Pubmed]
  12. Local administration of antisense phosphorothioate oligonucleotides to the p65 subunit of NF-kappa B abrogates established experimental colitis in mice. Neurath, M.F., Pettersson, S., Meyer zum Büschenfelde, K.H., Strober, W. Nat. Med. (1996) [Pubmed]
  13. Impaired defense of intestinal mucosa in mice lacking intestinal trefoil factor. Mashimo, H., Wu, D.C., Podolsky, D.K., Fishman, M.C. Science (1996) [Pubmed]
  14. Specific regulation of T helper cell 1-mediated murine colitis by CEACAM1. Iijima, H., Neurath, M.F., Nagaishi, T., Glickman, J.N., Nieuwenhuis, E.E., Nakajima, A., Chen, D., Fuss, I.J., Utku, N., Lewicki, D.N., Becker, C., Gallagher, T.M., Holmes, K.V., Blumberg, R.S. J. Exp. Med. (2004) [Pubmed]
  15. Carbon monoxide ameliorates chronic murine colitis through a heme oxygenase 1-dependent pathway. Hegazi, R.A., Rao, K.N., Mayle, A., Sepulveda, A.R., Otterbein, L.E., Plevy, S.E. J. Exp. Med. (2005) [Pubmed]
  16. Oxazolone colitis: A murine model of T helper cell type 2 colitis treatable with antibodies to interleukin 4. Boirivant, M., Fuss, I.J., Chu, A., Strober, W. J. Exp. Med. (1998) [Pubmed]
  17. Visceral pain perception is determined by the duration of colitis and associated neuropeptide expression in the mouse. Verma-Gandhu, M., Verdu, E.F., Bercik, P., Blennerhassett, P.A., Al-Mutawaly, N., Ghia, J.E., Collins, S.M. Gut (2007) [Pubmed]
  18. Fenofibrate represses interleukin-17 and interferon-gamma expression and improves colitis in interleukin-10-deficient mice. Lee, J.W., Bajwa, P.J., Carson, M.J., Jeske, D.R., Cong, Y., Elson, C.O., Lytle, C., Straus, D.S. Gastroenterology (2007) [Pubmed]
  19. The specificity of peptides bound to human histocompatibility leukocyte antigen (HLA)-B27 influences the prevalence of arthritis in HLA-B27 transgenic rats. Zhou, M., Sayad, A., Simmons, W.A., Jones, R.C., Maika, S.D., Satumtira, N., Dorris, M.L., Gaskell, S.J., Bordoli, R.S., Sartor, R.B., Slaughter, C.A., Richardson, J.A., Hammer, R.E., Taurog, J.D. J. Exp. Med. (1998) [Pubmed]
  20. 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. Kitani, A., Fuss, I.J., Nakamura, K., Schwartz, O.M., Usui, T., Strober, W. J. Exp. Med. (2000) [Pubmed]
  21. Galectin-1 suppresses experimental colitis in mice. Santucci, L., Fiorucci, S., Rubinstein, N., Mencarelli, A., Palazzetti, B., Federici, B., Rabinovich, G.A., Morelli, A. Gastroenterology (2003) [Pubmed]
  22. Therapeutic effects of rectal administration of basic fibroblast growth factor on experimental murine colitis. Matsuura, M., Okazaki, K., Nishio, A., Nakase, H., Tamaki, H., Uchida, K., Nishi, T., Asada, M., Kawasaki, K., Fukui, T., Yoshizawa, H., Ohashi, S., Inoue, S., Kawanami, C., Hiai, H., Tabata, Y., Chiba, T. Gastroenterology (2005) [Pubmed]
  23. Amelioration of dextran sulfate sodium-induced colitis by anti-macrophage migration inhibitory factor antibody in mice. Ohkawara, T., Nishihira, J., Takeda, H., Hige, S., Kato, M., Sugiyama, T., Iwanaga, T., Nakamura, H., Mizue, Y., Asaka, M. Gastroenterology (2002) [Pubmed]
  24. Induced reactivity of intestinal CD4(+) T cells with an epithelial cell lectin, galectin-4, contributes to exacerbation of intestinal inflammation. Hokama, A., Mizoguchi, E., Sugimoto, K., Shimomura, Y., Tanaka, Y., Yoshida, M., Rietdijk, S.T., de Jong, Y.P., Snapper, S.B., Terhorst, C., Blumberg, R.S., Mizoguchi, A. Immunity (2004) [Pubmed]
  25. Development of chronic colitis is dependent on the cytokine MIF. de Jong, Y.P., Abadia-Molina, A.C., Satoskar, A.R., Clarke, K., Rietdijk, S.T., Faubion, W.A., Mizoguchi, E., Metz, C.N., Alsahli, M., ten Hove, T., Keates, A.C., Lubetsky, J.B., Farrell, R.J., Michetti, P., van Deventer, S.J., Lolis, E., David, J.R., Bhan, A.K., Terhorst, C., Sahli, M.A. Nat. Immunol. (2001) [Pubmed]
  26. Transcriptional repressor Blimp-1 regulates T cell homeostasis and function. Martins, G.A., Cimmino, L., Shapiro-Shelef, M., Szabolcs, M., Herron, A., Magnusdottir, E., Calame, K. Nat. Immunol. (2006) [Pubmed]
  27. 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. Desreumaux, P., Dubuquoy, L., Nutten, S., Peuchmaur, M., Englaro, W., Schoonjans, K., Derijard, B., Desvergne, B., Wahli, W., Chambon, P., Leibowitz, M.D., Colombel, J.F., Auwerx, J. J. Exp. Med. (2001) [Pubmed]
  28. T helper cell 1-type CD4+ T cells, but not B cells, mediate colitis in interleukin 10-deficient mice. Davidson, N.J., Leach, M.W., Fort, M.M., Thompson-Snipes, L., Kühn, R., Müller, W., Berg, D.J., Rennick, D.M. J. Exp. Med. (1996) [Pubmed]
  29. Regulatory interactions between CD45RBhigh and CD45RBlow CD4+ T cells are important for the balance between protective and pathogenic cell-mediated immunity. Powrie, F., Correa-Oliveira, R., Mauze, S., Coffman, R.L. J. Exp. Med. (1994) [Pubmed]
  30. Nonlymphocyte-derived tumor necrosis factor is required for induction of colitis in recombination activating gene (RAG)2(-/-) mice upon transfer of CD4(+)CD45RB(hi) T cells. Corazza, N., Eichenberger, S., Eugster, H.P., Mueller, C. J. Exp. Med. (1999) [Pubmed]
  31. CIS3/SOCS3/SSI3 plays a negative regulatory role in STAT3 activation and intestinal inflammation. Suzuki, A., Hanada, T., Mitsuyama, K., Yoshida, T., Kamizono, S., Hoshino, T., Kubo, M., Yamashita, A., Okabe, M., Takeda, K., Akira, S., Matsumoto, S., Toyonaga, A., Sata, M., Yoshimura, A. J. Exp. Med. (2001) [Pubmed]
  32. The prostaglandin receptor EP4 suppresses colitis, mucosal damage and CD4 cell activation in the gut. Kabashima, K., Saji, T., Murata, T., Nagamachi, M., Matsuoka, T., Segi, E., Tsuboi, K., Sugimoto, Y., Kobayashi, T., Miyachi, Y., Ichikawa, A., Narumiya, S. J. Clin. Invest. (2002) [Pubmed]
  33. Gnotobiotic IL-10-/-;NF-kappa B(EGFP) mice reveal the critical role of TLR/NF-kappa B signaling in commensal bacteria-induced colitis. Karrasch, T., Kim, J.S., Muhlbauer, M., Magness, S.T., Jobin, C. J. Immunol. (2007) [Pubmed]
  34. Lymphocyte-dependent and Th2 cytokine-associated colitis in mice deficient in Wiskott-Aldrich syndrome protein. Nguyen, D.D., Maillard, M.H., Cotta-de-Almeida, V., Mizoguchi, E., Klein, C., Fuss, I., Nagler, C., Mizoguchi, A., Bhan, A.K., Snapper, S.B. Gastroenterology (2007) [Pubmed]
  35. Systemic, but not intestinal, IL-7 is essential for the persistence of chronic colitis. Tomita, T., Kanai, T., Nemoto, Y., Totsuka, T., Okamoto, R., Tsuchiya, K., Sakamoto, N., Watanabe, M. J. Immunol. (2008) [Pubmed]
  36. Experimental granulomatous colitis in mice is abrogated by induction of TGF-beta-mediated oral tolerance. Neurath, M.F., Fuss, I., Kelsall, B.L., Presky, D.H., Waegell, W., Strober, W. J. Exp. Med. (1996) [Pubmed]
  37. CD4+ T cells reactive to enteric bacterial antigens in spontaneously colitic C3H/HeJBir mice: increased T helper cell type 1 response and ability to transfer disease. Cong, Y., Brandwein, S.L., McCabe, R.P., Lazenby, A., Birkenmeier, E.H., Sundberg, J.P., Elson, C.O. J. Exp. Med. (1998) [Pubmed]
  38. Cross-organ sensitization of lumbosacral spinal neurons receiving urinary bladder input in rats with inflamed colon. Qin, C., Malykhina, A.P., Akbarali, H.I., Foreman, R.D. Gastroenterology (2005) [Pubmed]
  39. Chronic murine colitis is dependent on the CD154/CD40 pathway and can be attenuated by anti-CD154 administration. De Jong, Y.P., Comiskey, M., Kalled, S.L., Mizoguchi, E., Flavell, R.A., Bhan, A.K., Terhorst, C. Gastroenterology (2000) [Pubmed]
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