| First Author | Shah YM | Year | 2007 |
| Journal | Am J Physiol Gastrointest Liver Physiol | Volume | 292 |
| Issue | 2 | Pages | G657-66 |
| PubMed ID | 17095756 | Mgi Jnum | J:120606 |
| Mgi Id | MGI:3707287 | Doi | 10.1152/ajpgi.00381.2006 |
| Citation | Shah YM, et al. (2007) Expression of peroxisome proliferator-activated receptor-gamma in macrophage suppresses experimentally induced colitis. Am J Physiol Gastrointest Liver Physiol 292(2):G657-66 |
| abstractText | Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) has been shown to be a protective transcription factor in mouse models of inflammatory bowel disease (IBD). PPAR-gamma is expressed in several different cell types, and mice with a targeted disruption of the PPAR-gamma gene in intestinal epithelial cells demonstrated increased susceptibility to dextran sulfate sodium (DSS)-induced IBD. However, the highly selective PPAR-gamma ligand rosiglitazone decreased the severity of DSS-induced colitis and suppressed cytokine production in both PPAR-gamma intestinal specific null mice and wild-type littermates. Therefore the role of PPAR-gamma in different tissues and their contribution to the pathogenesis of IBD still remain unclear. Mice with a targeted disruption of PPAR-gamma in macrophages (PPAR-gamma(DeltaMphi)) and wild-type littermates (PPAR-gamma(F/F)) were administered 2.5% DSS in drinking water to induce IBD. Typical clinical symptoms were evaluated on a daily basis, and proinflammatory cytokine analysis was performed. PPAR-gamma(DeltaMphi) mice displayed an increased susceptibility to DSS-induced colitis compared with wild-type littermates, as defined by body weight loss, diarrhea, rectal bleeding score, colon length, and histology. IL-1beta, CCR2, MCP-1, and inducible nitric oxide synthase mRNA levels in colons of PPAR-gamma(DeltaMphi) mice treated with DSS were higher than in similarly treated PPAR-gamma(F/F) mice. The present study has identified a novel protective role for macrophage PPAR-gamma in the DSS-induced IBD model. The data suggest that PPAR-gamma regulates recruitment of macrophages to inflammatory foci in the colon. |
