Submitted to: Prostaglandins Leukotrienes and Essential Fatty Acids
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/26/2015
Publication Date: 5/20/2015
Citation: Honda, K.L., Lamon-Fava, S., Matthan, N., Wu, D., Lichtenstein, A.H. 2015. Docosahexaenoic acid differentially affects TNFalpha and IL-6 expression in LPS-stimulated RAW 264.7 murine macrophages. Prostaglandins Leukotrienes and Essential Fatty Acids. 97:27-34. https://doi.org/10.1016/j.plefa.2015.03.002. Interpretive Summary: Fish contains very long chain omega-3 fatty acids, one of which is docosahexaenoic acid (DHA). Higher intake of these fatty acids has been associated with lower risk of heart disease. This beneficial effect may in part be because of the decreased inflammatory response of cells that have higher levels of the very long chain omega-3 fatty acids. This study tested this hypothesis in a cell culture system. A macrophage cell line was used because these are the type of cells that are found in the blood vessel walls of individuals who have heart disease. Cultured macrophages were pretreated with a saturated fatty acid, myristic acid (MA), or DHA and then chemically stimulated. Treatment of the macrophages with DHA significantly reduced macrophages' inflammatory response in a dose-dependent manner. Prostaglandin (PG)E2 appeared to inhibit TNF-alpha expression, which is associated with inflammation. These data suggest that fatty acid profiles, particularly a long chain omega-3 fatty acid, DHA, influences cell inflammatory response in macrophages, resulting in lower risk of heart disease.
Technical Abstract: Docosahexaenoic acid (DHA) is generally reported to have anti-inflammatory properties, however, prior work has documented differential effects on individual pro-inflammatory cytokines: reduced IL-6, but not TNFalpha, mRNA expression in macrophages. To elucidate the mechanism, the roles of prostaglandin E2 (PGE2), cyclic AMP response element-binding protein (CREB), and NFkappaB were examined in RAW 264.7 macrophages. DHA did not influence CREB activity, but significantly reduced PGE2 production by 41% and NFkappaB activity by 32%. Exogenous PGE2 inhibited TNFalpha mRNA expression dose dependently. Unexpectedly, inhibiting PGE2 production with NS-398 also decreased TNFalpha mRNA expression, suggesting a concentration-dependent dual role of PGE2 in regulating TNFalpha expression. IL-6 expression was unaffected by endogenous or exogenous PGE2. Partial block of NFkappaB activation (SN50; 46%) or (BAY-11-7082; 41%) lowered IL-6 to a greater extent than TNFalpha mRNA expression. The differential effect of DHA on TNFalpha and IL-6 mRNA expression may be mediated via reduction in NFkappaB activity.