| First Author | Monk JM | Year | 2012 |
| Journal | Am J Physiol Gastrointest Liver Physiol | Volume | 302 |
| Issue | 1 | Pages | G153-67 |
| PubMed ID | 21940900 | Mgi Jnum | J:183340 |
| Mgi Id | MGI:5318434 | Doi | 10.1152/ajpgi.00315.2011 |
| Citation | Monk JM, et al. (2012) Immunomodulatory action of dietary fish oil and targeted deletion of intestinal epithelial cell PPARdelta in inflammation-induced colon carcinogenesis. Am J Physiol Gastrointest Liver Physiol 302(1):G153-67 |
| abstractText | The ligand-activated transcription factor peroxisome proliferator-activated receptor (PPAR)-delta is highly expressed in colonic epithelial cells; however, the role of PPARdelta 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 PPARdelta. Therefore, we assessed the role of PPARdelta in modulating the effects of dietary n-3 PUFAs by targeted deletion of intestinal epithelial cell PPARdelta (PPARdelta(DeltaIEpC)). 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 PPARdelta(DeltaIEpC) mice. FO reduced mucosal injury, tumor incidence, colonic STAT3 activation, and inflammatory cytokine gene expression, independent of PPARdelta genotype. CD8(+) T cell recruitment into MLNs was suppressed in PPARdelta(DeltaIEpC) mice. Similarly, FO reduced CD8(+) T cell numbers in the MLN. Dietary FO independently modulated MLN CD4(+) T cell activation status by decreasing CD44 expression. CD11a expression by MLN CD4(+) T cells was downregulated in PPARdelta(DeltaIEpC) mice. Lastly, splenic CD62L expression was downregulated in PPARdelta(DeltaIEpC) CD4(+) and CD8(+) T cells. These data demonstrate that expression of intestinal epithelial cell PPARdelta 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 PPARdelta-independent manner. |
