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

环孢菌素通过调节性T细胞调节肠粘膜TGF-β表达

• 批准号: 24790673
• 负责人: SAKURABA HIROTAKE
• 金额: $ 1.58万
• 依托单位: Hirosaki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2012
• 资助国家: 日本
• 起止时间: 2012-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-24790673/
• 关键词: 炎症性腸疾患; TGF-beta; 腸管上皮細胞; アポトーシス; シクロスポリン; 腸上皮アポトーシス; TGF-β; IL-22

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.

环孢素（CsA）在治疗溃疡性结肠炎方面表现出快速改善，但其确切机制仍不清楚。我们假设CsA会影响肠粘膜TGF-β的表达。通过在CD4+CD25+细胞转移的SCID小鼠中喂食4％DSS来诱导结肠炎。 CsA 治疗通过减少上皮细胞凋亡来改善粘膜破坏。 CsA 上调结肠中的 TGF-β。 SCID 小鼠中 TGF-β 表达显着受到抑制，CsA 治疗未能上调 TGF-β 表达。另一方面，CsA 治疗上调了 CD4+CD25+细胞转移 SCID 小鼠中的 TGF-β 表达。 然而，体外 CsA 处理并未增加分离的 CD4+CD25+ 细胞的 TGF-β 产量。这些结果表明，CsA 治疗可以通过 TGF-β 相关途径改善上皮损伤。 CD4+CD25+T细胞会通过TGF-β相关途径间接介导CsA的保护作用。

项目成果

Cyclosporine protects from apoptosis-mediated epithelial damage through epithelial STAT3 signaling pathway in DSS-induced colitis

环孢素通过上皮 STAT3 信号通路保护 DSS 诱导的结肠炎免受细胞凋亡介导的上皮损伤

• 发表时间: 2013
• 期刊: Inflammatory Bowel Disease 2013 Supplement
• 作者: Hirotake Sakuraba;Yoh Ishiguro;Hiroto Hiraga;Keisuke Hasui;Shinsaku Fukuda
• 通讯作者: Shinsaku Fukuda

Cyclosporine protects from apoptosis-mediated epithelial damage through epithelial STAT3 signaling pathway

环孢素通过上皮 STAT3 信号通路防止细胞凋亡介导的上皮损伤

• 发表时间: 2013
• 作者: Hirotake Sakuraba;Yoh Ishiguro;Hiroto Hiraga;Keisuke Hasui;Shinsaku Fukuda
• 通讯作者: Shinsaku Fukuda

Cyclosporine protects from apoptosis-mediated epithelial damage through epithelial STAT3 signaling pathway.

环孢素通过上皮 STAT3 信号通路防止细胞凋亡介导的上皮损伤。

• 发表时间: 2013
• 作者: Sawada Y;Yoshikawa T;Fujii S;Mitsunaga S;Nobuoka D;Mizuno S;Takahashi M;Yamauchi C;Endo I;Nakatsura T.;櫻庭 裕丈
• 通讯作者: 櫻庭 裕丈