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 (IFN gamma) 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 IFN gamma signaling in inflammatory cells Therefore. we have investigated the effects of DHA treatment on the ability of IFN gamma to induce CXCL16 expression in human aortic smooth muscle cells We observed that DHA treatment significantly reduced IFN gamma-induced CXCL16 expression As a result, the pro-atherosclerotic functions of CXCL16 were also inhibited Furthermore, IFN gamma-induced STAT1 phosphorylation was inhibited by DHA. Suggesting a potential mechanism In conclusion. Our data Suggest inhibition of IFN gamma signaling as one of the mechanisms behind the beneficial effects of DHA during atheroscleiosis. These findings may prove to be important in other disease fields that identify IFN gamma as a regulator. (C) 2009 Elsevier Inc All rights reserved.