The peroxisome proliferator-activated receptor γ (PPARγ) has been proposed as a key inhibitor of colitis through attenuation of nuclear factor κB (NF-κB) activity. In inflammatory bowel disease, activators of NF-κB, including the bacterial receptor toll-like receptor (TLR)4, are elevated. We aimed to determine the role of bacteria and their signaling effects on PPARγ regulation during inflammatory bowel disease (IBD).

TLR4-transfected Caco-2 cells, germ-free mice, and mice devoid of functional TLR4 (Lps^d/Lps^d mice) were assessed for their expression of PPARγ in colonic tissues in the presence or absence of bacteria. This nuclear receptor expression and the polymorphisms of gene also were assessed in patients with Crohn’s disease (CD) and ulcerative colitis (UC), 2 inflammatory bowel diseases resulting from an abnormal immune response to bacterial antigens.

TLR4-transfected Caco-2 cells showed that the TLR4 signaling pathway elevated PPARγ expression and a PPARγ-dependent reporter in an Iκκβ dependent fashion. Murine and human intestinal flora induced PPARγ expression in colonic epithelial cells of control mice. PPARγ expression was significantly higher in the colon of control compared with Lps^d/Lps^d mice. Although PPARγ levels appeared normal in patients with CD and controls, UC patients displayed a reduced expression of PPARγ confined to colonic epithelial cells, without any mutation in the PPARγ gene.

These data showed that the commensal intestinal flora affects the expression of PPARγ and that PPARγ expression is considerably impaired in patients with UC.