LAUSR

Abstract Phosphorylation and activation of p38 MAPK and NF&kgr;B pathways, along with the resulting overproduction of interleukin IL‐1&bgr;, IL‐6, and tumor necrosis factor a (TNF&agr;) is a hallmark of inflammatory disorders. Omega‐3 polyunsaturated fatty acid (n‐3 PUFA) supplementations are known to exert anti‐inflammatory properties by reduction of keys cytokines and enzymes involved in inflammation. Here, we investigated the anti‐inflammatory pathways and mediators modulated by eicosapentaenoic acid monoglyceride (MAG‐EPA) on human peripheral blood mononuclear cells (PBMCs) from healthy donors and stimulated, ex vivo, with lipopolysaccharide (LPS). LPS stimulation increased p38 MAPK and NF&kgr;B phosphorylation, which was abolished by MAG‐EPA treatments. Concomitantly, MAG‐EPA also abolished LPS‐induced inflammation in PBMCs by reducing IL‐1&bgr;, IL‐6, and TNF&agr; cytokines at protein and transcript levels. Moreover, MAG‐EPA decreased the levels of HIF1&agr; in LPS‐induced human PBMCs. Results also revealed a decreased of pro‐inflammatory enzymes such as Cyclooxygenase‐2 (COX‐2) and 5‐lipoxygenase (5‐LOX) in LPS‐induced PBMCs. Altogether, the present data suggest that MAG‐EPA, represents a new potential therapeutic strategy for resolving inflammation in inflammatory disorders including autoimmune diseases, allergies, asthma, arthritis and cancer.