Fish oil decreases macrophage tumor necrosis factor gene transcription by altering the NF-kappa B activity.

Author: Lo CJ, Chu KC, et al
Source: Journal of Surgical Research 82 (1999):216-221.
Publication Date: 4/1/1999

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Background.Fish oil-supplemented diets have anti-inflammatory and immunomodulating effects, though the exact mechanism(s) are unknown. This study investigated the effects of eicosapentanenoic acid (EPA), a major component of fish oil, on transcriptional regulation of tumor necrosis factor (TNF) gene in lipopolysaccharide (LPS)-stimulated macrophages (MØ). Methods.RAW 264.7 cells, a mouse MØ cell line, were grown in EPA-rich media for 24–48 h. MØ were washed and exposed toEscherichia coliLPS (1 µg/ml) for 2 h. TNF mRNA expression was measured by Northern blot assays. Total nuclear extracts were harvested for the measurement of NF?B with electrophoretic mobility shift assays. Supershift assays were performed with anti-P50 or anti-P65 antibodies to show components of NF?B dimers. TNF production was determined by L929 bioassays. Results.LPS stimulated RAW cell TNF mRNA expression and NF?B activity. In contrast, RAW cells grown in EPA-rich media had less TNF mRNA expression and an altered composition of the NF?B subunits (P65/P50 dimers) in the presence of LPS. TNF production by LPS-stimulated MØ was reduced by EPA. Conclusions.The inhibitory effect of EPA on LPS-stimulated MØ TNF gene transcription and protein elaboration is, in part, mediated through altering NF?B activation by reducing the P65/P50 dimers.