Cg. Su et al., A novel therapy for colitis utilizing PPAR-gamma ligands to inhibit the epithelial inflammatory response, J CLIN INV, 104(4), 1999, pp. 383-389
Peroxisome proliferator-activated receptor gamma (PPAK-gamma), a member of
the nuclear hormone receptor superfamily originally shown to play a critica
l role in adipocyte differentiation and glucose homeostasis, has recently b
een implicated as a regulator of cellular proliferation and inflammatory re
sponses. 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 l
igands dramatically attenuate cytokine gene expression in colon cancer cell
lines by inhibiting the activation of nuclear factor-kappa B via an I kapp
a 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 huma
ns suffering from IBD.