Docosahexaenoic acid differentially affects TNFα and IL-6 expression in LPS-stimulated RAW 264.7 murine macrophages.
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.
Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, Boston, MA 02111, USA.
Kaori L
KL
Honda
Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, Boston, MA 02111, USA.
Stefania
S
Lamon-Fava
Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, Boston, MA 02111, USA.
Nirupa R
NR
Matthan
Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, Boston, MA 02111, USA.
Dayong
D
Wu
Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, Boston, MA 02111, USA. Electronic address: alice.lichtenstein@tufts.edu.
Alice H
AH
Lichtenstein
D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D015232:Dinoprostone / Q000378:metabolism / Q000494:pharmacology; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects; D015850:Interleukin-6 / Q000235:genetics*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D009578:Nitrobenzenes / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013449:Sulfonamides / Q000494:pharmacology; D013450:Sulfones / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
C434003:3-(4-methylphenylsulfonyl)-2-propenenitrile; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009570:Nitriles; D009578:Nitrobenzenes; D010455:Peptides; D012333:RNA, Messenger; C118258:SN50 peptide; D013449:Sulfonamides; D013450:Sulfones; D014409:Tumor Necrosis Factor-alpha; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D004281:Docosahexaenoic Acids; D015232:Dinoprostone
CREB; IL-6; Macrophages; PGE(2); TLR4; TNFα