Cyclosporin regulates TGF-beta expression of intestinal mucosa by regulatory T cells

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Cyclosporine (CsA) showed a rapid improvement in the treatment of ulcerative colitis, but the precise mechanism is still obscure. We hypothesized that CsA would affect the TGF-beta expression of intestinal mucosa. Colitis was induced by feeding of 4% DSS in CD4+CD25+cells-transferred SCID mice. Treatment of CsA ameliorated mucosal destruction through reduction of epithelial apoptosis. CsA up-regulated the TGF-beta in the colon. TGF-beta expression was significantly suppressed and treatment of CsA failed to up-regulate the expression of TGF-beta in SCID mice. On the other hand, treatment of CsA up-regulated TGF-beta expression in CD4+CD25+cells-transferred SCID mice. However, TGF-beta production from separated-CD4+CD25+cells was not increased by treatment of CsA in vitro. These results demonstrate that treatment of CsA can ameliorate epithelial damage through TGF-beta-related pathway. CD4+CD25+T cells would indirectly mediate the protective effect of CsA via TGF-beta-related pathway.