Keith Wilson
Faculty Member
Last active: 12/19/2020

Peroxisome proliferator-activated receptor δ promotes colonic inflammation and tumor growth.

Wang D, Fu L, Ning W, Guo L, Sun X, Dey SK, Chaturvedi R, Wilson KT, DuBois RN
Proc Natl Acad Sci U S A. 2014 111 (19): 7084-9

PMID: 24763687 · PMCID: PMC4024916 · DOI:10.1073/pnas.1324233111

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 δ (PPARδ) attenuates colonic inflammation and colitis-associated adenoma formation/growth. Importantly, PPARδ 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 PPARδ 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 PPARδ 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.

MeSH Terms (18)

Adenoma Animals Cell Communication Cell Line, Tumor Colitis Colorectal Neoplasms Cyclooxygenase 2 Dextran Sulfate Dietary Fats Dinoprostone Epithelial Cells Humans Macrophages Male Mice Mice, Knockout Monocytes Receptors, Cytoplasmic and Nuclear

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