title: Comparison of experimental mouse models of inflammatory bowel disease.
abstract: Inflammatory bowel disease (IBD) is multifactorial and involves immunological, environmental and genetic factors. Although there are no animal models that effectively mimic human IBD, experimental models allow us to analyze the mechanisms of chronic intestinal inflammation. IBD can be induced in mice by dextran sulfate sodium (DSS) or by a 2,4,6-trinitrobenzene sulfonic acid (TNBS)‑ethanol enema, which evoke immune responses and colitis. In this study, in order to compare the mechanisms of inflammatory response in mice, 3 distinct models of IBD were established: 2% TNBS-induced acute colitis, 4% DSS-induced acute colitis and 2% DSS-induced chronic colitis. In addition, to evaluate the effects of TNBS on inflammasome activation, we used caspase-1 knockout (KO) mice. Changes in both body weight and survival became prominent after day 1 in the 2% TNBS‑induced colitis model, and after day 5 in the 4% DSS-induced colitis model. The TNBS- and DSS-treated mice, but not the caspase-1 KO mice, showed a massive bowel edema and disruption of epithelial cells. The level of CD11b(+)Gr-1(+) myeloid-derived suppressor cells (MDSCs) was increased in all tested tissues of the TNBS- and DSS-treated groups, apart from the basal membrane (BM) in the DSS-induced colitis groups and the lamina propria (LP) in the DSS-induced chronic colitis group. We further analyzed different subsets of CD4(+) T cells in LP and found that the levels of interferon (IFN)γ‑secreting (IFNγ(+)), IL-17‑secreting (IL-17(+)), but not those of IL-4-secreting (IL-4(+)) T cells increased upon treatment with TNBS or DSS. In addition, discrepancies between the histopathologies of wild-type and caspase-1 KO mice indicated that the pathogenesis of IBD may be associated with the inflammasome pathway responses mediated by caspase‑1 in TNBS‑induced colitis.
authors.affiliation: Department of Surgery, School of Medicine, Ewha Womans University, Seoul 158-710, Republic of Korea.
authors.forename: Soo Youn
authors.initials: SY
authors.lastname: Oh
authors.affiliation: Department of Microbiology, School of Medicine, Ewha Womans University, Seoul 158-710, Republic of Korea.
authors.forename: Kyung-Ah
authors.initials: KA
authors.lastname: Cho
authors.affiliation: Department of Physiology, School of Medicine, Ewha Womans University, Seoul 158-710, Republic of Korea.
authors.forename: Jihee Lee
authors.initials: JL
authors.lastname: Kang
authors.affiliation: Department of Surgery, School of Medicine, Ewha Womans University, Seoul 158-710, Republic of Korea.
authors.forename: Kwang Ho
authors.initials: KH
authors.lastname: Kim
authors.affiliation: Department of Microbiology, School of Medicine, Ewha Womans University, Seoul 158-710, Republic of Korea.
authors.forename: So-Youn
authors.initials: SY
authors.lastname: Woo
mesh_terms: D000208:Acute Disease; D000818:Animals; D020170:Caspase 1 / Q000235:genetics / Q000378:metabolism; D002908:Chronic Disease; D003092:Colitis / Q000139:chemically induced / Q000473:pathology*; D016264:Dextran Sulfate / Q000009:adverse effects; D004195:Disease Models, Animal; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced / Q000473:pathology*; D015847:Interleukin-4 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013601:T-Lymphocytes / Q000187:drug effects / Q000378:metabolism; D014302:Trinitrobenzenesulfonic Acid / Q000009:adverse effects
chemical_list: D015847:Interleukin-4; D014302:Trinitrobenzenesulfonic Acid; D016264:Dextran Sulfate; D020170:Caspase 1