Peroxisome proliferator-activated receptor ä promotes colonic inflammation and tumor growth

Dingzhi Wang, Lingchen Fu, Wei Ning, Lixia Guo, Xiaofei Sun, Sudhansu K. Dey, Rupesh Chaturvedi, Keith T. Wilson, Raymond N. DuBois

    Research output: Contribution to journalArticle

    38 Scopus citations

    Abstract

    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 ä (PPARä) attenuates colonic inflammation and colitis-associated adenoma formation/growth. Importantly, PPARä is required for dextran sodium sulfate induction of proinflammatory mediators, including chemokines, cytokines, COX-2, and prostaglandin E 2 (PGE2), in vivo. We further show that activation of PPARä induces COX-2 expression in colonic epithelial cells. COX-2-derived PGE 2 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 PPARä 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.

    Original languageEnglish (US)
    Pages (from-to)7084-7089
    Number of pages6
    JournalProceedings of the National Academy of Sciences of the United States of America
    Volume111
    Issue number19
    DOIs
    StatePublished - May 13 2014

    Keywords

    • COX-2/PGE2
    • Colorectal cancer

    ASJC Scopus subject areas

    • General

    Fingerprint Dive into the research topics of 'Peroxisome proliferator-activated receptor ä promotes colonic inflammation and tumor growth'. Together they form a unique fingerprint.

  • Cite this