Docosahexaenoic acid downregulates interferon gamma-induced expression of CXCL16 in human aortic smooth muscle cells.
CXCL16 is a chemokine that is expressed in both transmembrane and secreted isoforms. Both variants have been implicated in atherosclerosis. Increased CXCL16 expression on the surface of human aortic smooth muscle cells induced by interferon gamma (IFNgamma) signaling results in enhanced oxidized low density lipoprotein uptake and enhanced recruitment of pro-inflammatory cells. Docosahexaenoic acid (DHA), an omega-3 fatty acid, is known to inhibit IFNgamma signaling in inflammatory cells. Therefore, we have investigated the effects of DHA treatment on the ability of IFNgamma to induce CXCL16 expression in human aortic smooth muscle cells. We observed that DHA treatment significantly reduced IFNgamma-induced CXCL16 expression. As a result, the pro-atherosclerotic functions of CXCL16 were also inhibited. Furthermore, IFNgamma-induced STAT1 phosphorylation was inhibited by DHA, suggesting a potential mechanism. In conclusion, our data suggest inhibition of IFNgamma signaling as one of the mechanisms behind the beneficial effects of DHA during atherosclerosis. These findings may prove to be important in other disease fields that identify IFNgamma as a regulator.
Altenburg
Jeffrey D
JD
Cellular Biochemistry Laboratory, Methodist Research Institute, Clarian Health Partners, Indianapolis, IN 46202, United States. jaltenbu@clarian.org
Siddiqui
Rafat A
RA
D001011:Aorta / Q000187:drug effects* / Q000378:metabolism; D050197:Atherosclerosis / Q000188:drug therapy / Q000378:metabolism; D002478:Cells, Cultured; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D002633:Chemotaxis / Q000187:drug effects; D004281:Docosahexaenoic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D015536:Down-Regulation; D006801:Humans; D007371:Interferon-gamma / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation; D051116:Receptors, Scavenger / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D050794:STAT1 Transcription Factor / Q000378:metabolism
C423727:CXCL16 protein, human; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC; D008077:Lipoproteins, LDL; D051116:Receptors, Scavenger; D050794:STAT1 Transcription Factor; C099252:oxidized low density lipoprotein; D004281:Docosahexaenoic Acids; D007371:Interferon-gamma