Protective effects of tranilast on oxazolone-induced rat colitis through a mast cell-dependent pathway.

Mast cells in the gut play an important role in the innate and adaptive immune responses that are relevant to human inflammatory bowel disease. However, the contribution of mast cells to the development of inflammatory bowel disease is not well understood. This study aimed to determine the role of mast cells in oxazolone-induced colitis and to explore whether the mast cell membrane stabiliser tranilast could ameliorate colonic inflammation. Wild-type rats and mast cell-deficient rats were sensitised and challenged with oxazolone, then treated with tranilast after challenge. Controls were treated with saline. Mast cell-deficient rats presented a weak response to oxazolone, while wild-type rats showed severe ulcerative colitis after stimulation with oxazolone. The mast cell-deficient rats model had a significantly lower disease activity index score than wild-type rats model (1.8±1.64 vs. 8.3±0.58 respectively; P<0.01). Tranilast could reduce the secretion of cytokines, immunoglobulins and myeloperoxidase activity in tranilast treatment groups compared with the model group. The number of mast cells in the wild-type model was higher than in the other groups. There was no significant change in mast cell-deficient rats. Mast cells play an important role in oxazolone-induced colitis. The mast cell membrane stabiliser tranilast can ameliorate oxazolone-induced colitis via a mast cell-dependent pathway.

Chu HQ ，Li J ，Huang HP ，Hao WD ，Duan LP ，Wei XT ... -  《-》

Rectal administration of tranilast ameliorated acute colitis in mice through increased expression of heme oxygenase-1.

Sun X ，Suzuki K ，Nagata M ，Kawauchi Y ，Yano M ，Ohkoshi S ，Matsuda Y ，Kawachi H ，Watanabe K ，Asakura H ，Aoyagi Y ... -  《-》

Synergistic effect of κ-carrageenan on oxazolone-induced inflammation in BALB/c mice.

Wu W ，Wang F ，Gao X ，Niu T ，Zhu X ，Yan X ，Chen H ... -  《BMC GASTROENTEROLOGY》

B cells that produce immunoglobulin E mediate colitis in BALB/c mice.

Induction of colitis in mice by administration of oxazolone is mediated by T-helper (Th) 2 cells and has features of human ulcerative colitis. We investigated whether activation of interleukin (IL)-4Rα on T and B cells determines their effector functions and mediates oxazolone-induced colitis. We studied induction of colitis with oxazolone in wild-type mice and those with CD4(+) T cells that did not express IL-4Rα (Lck(cre)IL-4Rα(-/lox)). We also generated mice with B cells that did not express IL-4Rα (mb1(cre)IL-4Rα(-/lox)) and studied induction of colitis. Lck(cre)IL-4Rα(-/lox) mice did not develop colitis in response to oxazolone, and their levels of IL-4, IL-13, and immunoglobulin (Ig) E were reduced. Adoptive transfer of naïve, wild-type CD4(+) Th cells depleted of natural killer T cells to Lck(cre)IL-4Rα(-/lox) mice restored their susceptibility to colitis. In contrast, Lck(cre)IL-4Rα(-/lox) mice maintained their protection against colitis when IL-13-deficient CD4(+) T cells were transferred. These findings indicate that development of colitis involves not only natural killer T-cell functions, but also requires IL-13 production by CD4(+) T helper cells. Mb1(cre)IL-4Rα(-/lox) mice, which cannot produce IgE, were also protected against oxazolone-induced colitis. Blocking IgE binding significantly reduced mast cell numbers in colons and protected wild-type BALB/c mice from the onset of colitis. IL-4 appears to induce CD4(+) Th2 cells to produce IL-13 and B cells to produce IgE, which together mediate oxazolone-induced colitis in mice.

Hoving JC ，Kirstein F ，Nieuwenhuizen NE ，Fick LC ，Hobeika E ，Reth M ，Brombacher F ... -  《-》

Helminth infection enhances disease in a murine TH2 model of colitis.

Hunter MM ，Wang A ，McKay DM 《GASTROENTEROLOGY》