A novel therapy for colitis utilizing PPAR-γ ligands to inhibit the epithelial inflammatory response

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Abstract

Peroxisome proliferator-activated receptor γ (PPAR-γ), 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-γ protein, have the ability to produce inflammatory cytokines that may play a role in inflammatory bowel disease (IBD). We report here that PPAR-γ ligands dramatically attenuate cytokine gene expression in colon cancer cell lines by inhibiting the activation of nuclear factor-κB via an IκB-α–dependent mechanism. Moreover, thiazolidinedione ligands for PPAR-γ markedly reduce colonic inflammation in a mouse model of IBD. These results suggest that colonic PPAR-γ may be a therapeutic target in humans suffering from IBD.

Authors

Chinyu G. Su, Xiaoming Wen, Shannon T. Bailey, Wen Jiang, Shamina M. Rangwala, Sue A. Keilbaugh, Anne Flanigan, Sreekant Murthy, Mitchell A. Lazar, Gary D. Wu