Differential Effects of Prostaglandin Derived from ω-6 and ω-3 Polyunsaturated Fatty Acids on COX-2 Expression and IL-6 Secretion

• Published in: Proceedings of the National Academy of Sciences - PNAS 2003-02, Vol.100 (4), p.1751-1756
• Main Authors: Bagga, Dilprit, Wang, Ling, Farias-Eisner, Robin, Glaspy, John A., Reddy, Srinivasa T.
• Format: Article
• Language: English
• Subjects: 3T3 Cells; Alprostadil - analogs & derivatives; Alprostadil - pharmacology; Animals; Biological Sciences; Blotting, Northern; Blotting, Western; Cell growth; Cell membranes; Cyclooxygenase 2; Dinoprostone - pharmacology; Effects; Fatty acids; Fatty Acids, Omega-3 - chemistry; Fatty Acids, Omega-6; Fatty Acids, Unsaturated - chemistry; Fibroblasts; Interleukin-6 - biosynthesis; Interleukin-6 - secretion; Isoenzymes - genetics; Macrophages; Macrophages - secretion; Mice; NIH 3T3 cells; Prostaglandin-Endoperoxide Synthases - genetics; Prostaglandins; RNA, Messenger - genetics; Secretion; Transcriptional Activation; Unsaturated fatty acids
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0334211100

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). PGE2, 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., PGE3), 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 PGE2and PGE3on (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. PGE3, unlike PGE2, is not mitogenic to NIH 3T3 fibroblasts. PGE2and PGE3both induce COX-2 mRNA via similar signaling mechanisms; however, compared with PGE2, PGE3is significantly less efficient in inducing COX-2 gene expression. Furthermore, although both PGE2and PGE3induce IL-6 synthesis in RAW 264.7 macrophages, PGE3is substantially less efficient compared with PGE2. We further show that increasing the ω-3 content of membrane phospholipid results in a decrease in mitogen-induced PGE2synthesis. 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.