A novel therapy for colitis utilizing PPAR-γ ligands to inhibit the epithelial inflammatory response
A novel therapy for colitis utilizing PPAR-γ ligands to inhibit the epithelial inflammatory response
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DOI：
10.1172/jci7145
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发表时间：
1999-08-01
影响因子：
15.9
通讯作者：
Wu, GD
中科院分区：
文献类型：
--
作者：
Su, CG;Wen, XM;Wu, GD
过氧化物酶体增殖物激活受体γ（PPAK-γ）是核激素受体超家族的成员，最初被证明在脂肪细胞分化和葡萄糖稳态中起关键作用，最近被认为是细胞增殖和炎症反应的调节剂。表达高水平PPAR-gamma蛋白的结肠上皮细胞具有产生可能在炎症性肠病（IBD）中起作用的炎性细胞因子的能力。我们在这里报告，PPAR-gamma配体通过抑制核因子-κ B-α依赖性机制激活核因子-κ B，显著减弱结肠癌细胞系中细胞因子基因的表达。此外，PPAR-γ的噻唑烷二酮配体显著降低IBD小鼠模型中的结肠炎症。这些结果表明，结肠PPAR-gamma可能是患有IBD的人的治疗靶点。
Peroxisome proliferator-activated receptor gamma (PPAK-gamma), a member of the nuclear hormone receptor superfamily originally shown to play a critical role in adipocyte differentiation and glucose homeostasis, has recently been implicated as a regulator of cellular proliferation and inflammatory responses. Colonic epithelial cells, which express high levels of PPAR-gamma protein, have the ability to produce inflammatory cytokines that may play a role in inflammatory bowel disease (IBD). We report here that PPAR-gamma ligands dramatically attenuate cytokine gene expression in colon cancer cell lines by inhibiting the activation of nuclear factor-kappa B via an I kappa B-alpha-dependent mechanism. Moreover, thiazolidinedione ligands for PPAR-gamma markedly reduce colonic inflammation in a mouse model of IBD. These results suggest that colonic PPAR-gamma may be a therapeutic target in humans suffering from IBD.