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B inhibition by 
-3 fatty acids modulates
LPS-stimulated macrophage TNF-
transcription
Laboratories of Surgical Metabolism, University of Illinois at Chicago, Chicago, Illinois 60612
-3 Fatty acid (FA) emulsions
reduce LPS-stimulated murine macrophage TNF-
production, but the
exact mechanism has yet to be defined. The purpose of this study was to
determine the mechanism for -3 FA inhibition of macrophage TNF-
production following LPS stimulation. RAW 264.7 cells were pretreated
with isocaloric emulsions of -3 FA (Omegaven), -6 FA (Lipovenos),
or DMEM and subsequently exposed to LPS. I
B- and
phospho-IB- were determined by Western blotting. NF-B binding
was assessed using the electromobility shift assay, and activity was
measured using a luciferase reporter vector. RT-PCR and ELISA
quantified TNF- mRNA and protein levels, respectively. Pretreatment
with -3 FA inhibited IB phosphorylation and significantly
decreased NF-B activity. Moreover, -3-treated cells demonstrated
significant decreases in both TNF- mRNA and protein expression by 47 and 46%, respectively. These experiments demonstrate that a mechanism
for proinflammatory cytokine inhibition in murine macrophages by -3
FA is mediated, in part, through inactivation of the NF-B signal
transduction pathway secondary to inhibition of IB phosphorylation.
eicosapentaenoic acid; nuclear factor-B; signal transduction; tumor necrosis factor-
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