A Novel Therapy for Colitis Utilizing PPAR-gamma Ligands to Inhibit the Epithelial Inflammatory Response

Overview

Journal J Clin Invest

Specialty General Medicine

Date 1999 Aug 17

PMID 10449430

Citations 200

Authors

C G Su

X Wen

S T Bailey

W Jiang

S M Rangwala

S A Keilbaugh

A Flanigan

S Murthy

M A Lazar

G D Wu

Affiliations

Soon will be listed here.

Abstract

Peroxisome proliferator-activated receptor gamma (PPAR-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-kappaB via an IkappaB-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.

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