Docosahexaenoic acid differentially affects TNFα and IL-6 expression in LPS-stimulated RAW 264.7 murine macrophages. (June 2015)

• Record Type: Journal Article
• Authors: Honda, Kaori L.; Lamon-Fava, Stefania; Matthan, Nirupa R.; Wu, Dayong; Lichtenstein, Alice H.
• Is Part Of: Prostaglandins, leukotrienes, and essential fatty acids. Volume 97(2015:Jun.)
• Page Start: 27
• Page End: 34
• Publication Date: 2015-06
• Subjects: TNFα -- IL-6 -- TLR4 -- Macrophages -- PGE2 -- CREB; Lipids -- Periodicals; Unsaturated fatty acids -- Periodicals; Prostaglandins -- Periodicals; Leukotrienes -- Periodicals; Fatty Acids, Unsaturated -- Periodicals; Acides gras insaturés -- Périodiques; Prostaglandines -- Périodiques; Leucotriènes -- Périodiques; Lipides -- Périodiques; 612.01577
• DOI: 10.1016/j.plefa.2015.03.002
• Languages: English
• ISSNs: 0952-3278

Abstract

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 TNFα, mRNA expression in macrophages. To elucidate the mechanism, the roles of prostaglandin E2 (PGE2 ), cyclic AMP response element-binding protein (CREB), and NFκB were examined in RAW 264.7 macrophages. DHA did not influence CREB activity, but significantly reduced PGE2 production by 41% and NFκB activity by 32%. Exogenous PGE2 inhibited TNFα mRNA expression dose dependently. Unexpectedly, inhibiting PGE2 production with NS-398 also decreased TNFα mRNA expression, suggesting a concentration-dependent dual role of PGE2 in regulating TNFα expression. IL-6 expression was unaffected by endogenous or exogenous PGE2 . Partial block of NFκB activation (SN50; 46%, or, BAY-11-7082; 41%) lowered IL-6 to a greater extent than TNFα mRNA expression. The differential effect of DHA on TNFα and IL-6 mRNA expression may be mediated via reduction in NFκB activity.