{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:49:29Z","timestamp":1787017769204,"version":"build-2736575974"},"reference-count":104,"publisher":"American Physiological Society","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Gastrointestinal and Liver Physiology"],"published-print":{"date-parts":[[2012,1]]},"abstract":"<jats:p>\n                    The ligand-activated transcription factor peroxisome proliferator-activated receptor (PPAR)-\u03b4 is highly expressed in colonic epithelial cells; however, the role of PPAR\u03b4 ligands, such as fatty acids, in mucosal inflammation and malignant transformation has not been clarified. Recent evidence suggests that the anti-inflammatory\/chemoprotective properties of fish oil (FO)-derived n-3 polyunsaturated fatty acids (PUFAs) may be partly mediated by PPAR\u03b4. Therefore, we assessed the role of PPAR\u03b4 in modulating the effects of dietary n-3 PUFAs by targeted deletion of intestinal epithelial cell PPAR\u03b4 (PPAR\u03b4\n                    <jats:sup>\u0394IEpC<\/jats:sup>\n                    ). Subsequently, we documented changes in colon tumorigenesis and the inflammatory microenvironment, i.e., local [mesenteric lymph node (MLN)] and systemic (spleen) T cell activation. Animals were fed chemopromotive [corn oil (CO)] or chemoprotective (FO) diets during the induction of chronic inflammation\/carcinogenesis. Tumor incidence was similar in control and PPAR\u03b4\n                    <jats:sup>\u0394IEpC<\/jats:sup>\n                    mice. FO reduced mucosal injury, tumor incidence, colonic STAT3 activation, and inflammatory cytokine gene expression, independent of PPAR\u03b4 genotype. CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell recruitment into MLNs was suppressed in PPAR\u03b4\n                    <jats:sup>\u0394IEpC<\/jats:sup>\n                    mice. Similarly, FO reduced CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell numbers in the MLN. Dietary FO independently modulated MLN CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell activation status by decreasing CD44 expression. CD11a expression by MLN CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells was downregulated in PPAR\u03b4\n                    <jats:sup>\u0394IEpC<\/jats:sup>\n                    mice. Lastly, splenic CD62L expression was downregulated in PPAR\u03b4\n                    <jats:sup>\u0394IEpC<\/jats:sup>\n                    CD4\n                    <jats:sup>+<\/jats:sup>\n                    and CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells. These data demonstrate that expression of intestinal epithelial cell PPAR\u03b4 does not influence azoxymethane\/dextran sodium sulfate-induced colon tumor incidence. Moreover, we provide new evidence that dietary n-3 PUFAs attenuate intestinal inflammation in an intestinal epithelial cell PPAR\u03b4-independent manner.\n                  <\/jats:p>","DOI":"10.1152\/ajpgi.00315.2011","type":"journal-article","created":{"date-parts":[[2011,9,23]],"date-time":"2011-09-23T02:03:31Z","timestamp":1316743411000},"page":"G153-G167","source":"Crossref","is-referenced-by-count":21,"title":["Immunomodulatory action of dietary fish oil and targeted deletion of intestinal epithelial cell PPAR\u03b4 in inflammation-induced colon carcinogenesis"],"prefix":"10.1152","volume":"302","author":[{"given":"Jennifer M.","family":"Monk","sequence":"first","affiliation":[{"name":"Program in Integrative Nutrition and Complex Diseases,"},{"name":"Intercollegiate Faculty of Nutrition, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wooki","family":"Kim","sequence":"additional","affiliation":[{"name":"Program in Integrative Nutrition and Complex 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