Omega-6 (ω-6) polyunsaturated fatty acids (PUFA), abundant in the Western diet, are precursors for a number of key mediators of inflammation including the 2-series of prostaglandins (PG). PGE 2 , a cyclooxygenase (COX) metabolite of arachidonic acid, a ω-6 PUFA, is a potent mediator of inflammation and cell proliferation. Dietary supplements rich in ω-3 PUFA reduce the concentrations of 2-series PG and increase the synthesis of 3-series PG (e.g., PGE 3 ), which are believed to be less inflammatory. However, studies on cellular consequences of increases in 3-series PG in comparison to 2-series PG have not been reported. In this study, we compared the effects of PGE 2 and PGE 3 on ( i ) cell proliferation in NIH 3T3 fibroblasts, ( ii ) expression and transcriptional regulation of the COX-2 gene in NIH 3T3 fibroblasts, and ( iii ) the production of an inflammatory cytokine, IL-6, in RAW 264.7 macrophages. PGE 3 , unlike PGE 2 , is not mitogenic to NIH 3T3 fibroblasts. PGE 2 and PGE 3 both induce COX-2 mRNA via similar signaling mechanisms; however, compared with PGE 2 , PGE 3 is significantly less efficient in inducing COX-2 gene expression. Furthermore, although both PGE 2 and PGE 3 induce IL-6 synthesis in RAW 264.7 macrophages, PGE 3 is substantially less efficient compared with PGE 2 . We further show that increasing the ω-3 content of membrane phospholipid results in a decrease in mitogen-induced PGE 2 synthesis. Taken together, our data suggest that successful replacement of ω-6 PUFA with ω-3 PUFA in cell membranes can result in a decreased cellular response to mitogenic and inflammatory stimuli.

Differential effects of prostaglandin derived from ω-6 and ω-3 polyunsaturated fatty acids on COX-2 expression and IL-6 secretion