Contrasting Effects of n‐3 EPA vs. Palmitic Acid on Endothelial Lipase and Inflammatory Cytokines in Murine Macrophages In Vitro

Abstract

Endothelial lipase (EL) links to increased inflammatory responses and atherogenesis. Because of its anti‐inflammatory properties we hypothesized that an n‐3 fatty acid (FA), EPA, in contrast to saturated palmitic acid (PA), would lower lipase and inflammatory markers in cells that produce EL, i.e., murine J774 and peritoneal macrophages (from C57BL/6 mice). Cells were cultured +/‐ lipopolysaccaride (LPS), 1 μg/ml, for 4‐21h after preincubation with increasing concentrations of PA or EPA for 3h. EL, IL‐6, IL‐12 and IL‐10 were assayed by RT‐PCR, and EL by Western analyses. LPS alone increased EL mRNA (>2.5 fold). PA alone as well as with LPS dose dependently increased EL mRNA by >2.5 fold. EPA totally abrogated effects of LPS on increasing EL mRNA. EL protein levels showed similar responses to LPS and to PA vs. EPA. EPA alone or with LPS also decreased pro‐inflammatory IL‐6 and IL‐12 mRNA by 70% and increased anti‐inflammatory IL‐10 mRNA (>2 fold), whereas PA decreased (by 46 %) IL‐10 mRNA (All p<0.05). Thus, n‐3 EPA has strong antiatherogenic compared to proatherogenic effects of PA in cells important in atherogenesis. We hypothesize that suppression of arterial EL and pro‐inflammatory cytokines with activation of anti‐inflammatory cytokines are important pathways underlying the effects of n‐3 FA in reducing cardiovascular events in humans.