| First Author | Wang D | Year | 2014 |
| Journal | Proc Natl Acad Sci U S A | Volume | 111 |
| Issue | 19 | Pages | 7084-9 |
| PubMed ID | 24763687 | Mgi Jnum | J:211077 |
| Mgi Id | MGI:5573100 | Doi | 10.1073/pnas.1324233111 |
| Citation | Wang D, et al. (2014) Peroxisome proliferator-activated receptor delta promotes colonic inflammation and tumor growth. Proc Natl Acad Sci U S A 111(19):7084-9 |
| abstractText | Although epidemiologic and experimental evidence strongly implicates chronic inflammation and dietary fats as risk factors for cancer, the mechanisms underlying their contribution to carcinogenesis are poorly understood. Here we present genetic evidence demonstrating that deletion of peroxisome proliferator-activated receptor delta (PPARdelta) attenuates colonic inflammation and colitis-associated adenoma formation/growth. Importantly, PPARdelta is required for dextran sodium sulfate induction of proinflammatory mediators, including chemokines, cytokines, COX-2, and prostaglandin E2 (PGE2), in vivo. We further show that activation of PPARdelta induces COX-2 expression in colonic epithelial cells. COX-2-derived PGE2 stimulates macrophages to produce proinflammatory chemokines and cytokines that are responsible for recruitment of leukocytes from the circulation to local sites of inflammation. Our results suggest that PPARdelta promotes colonic inflammation and colitis-associated tumor growth via the COX-2-derived PGE2 signaling axis that mediates cross-talk between tumor epithelial cells and macrophages. |
