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, 23 (1), 71-8

Eicosapentaenoic Acid Prevents LPS-induced TNF-alpha Expression by Preventing NF-kappaB Activation

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Eicosapentaenoic Acid Prevents LPS-induced TNF-alpha Expression by Preventing NF-kappaB Activation

Yan Zhao et al. J Am Coll Nutr.

Abstract

Background: Many studies have shown that fish oil supplementation inhibits tumor necrosis factor-alpha (TNF-alpha) production in mice and human subjects; however, the mechanisms remain unclear. Nuclear factor-kappaB (NF-kappaB) is a transcription factor that plays an important role in controlling the expression of pro-inflammatory genes including TNF-alpha. Activation of NF-kappaB has been shown to mediate the maximal expression of TNF-alpha in human monocytes. NF-kappaB is kept in an inactive form in the cytoplasm by IkappaB, the inhibitory subunit of NF-kappaB complex. Phosphorylation and subsequent degradation of IkappaB lead to NF-kappaB activation.

Objectives: The effect of eicosapentaenoic acid (EPA), a major n-3 fatty acid in fish oil, on the lipopolysaccharide (LPS)-induced expression of TNF-alpha and activation of NF-kappaB were investigated. The mechanism underlying EPA modulation of NF-kappaB activation was also studied.

Methods: Human monocytic THP-1 cells were pre-incubated with EPA and stimulated with LPS. The levels of secreted TNF-alpha were determined by ELISA. The DNA binding activity of NF-kappaB was analyzed by EMSA. The degradation and phosphorylation of IkappaB-alpha were examined by Western blot analysis.

Results: TNF-alpha production and expression induced by LPS were significantly decreased in cells pre-incubated with EPA. LPS-induced NF-kappaB activation, translocation of p65 subunit to the nucleus, phosphorylation and degradation of IkappaB-alpha were partially prevented by EPA.

Conclusions: The results suggest that suppression of the TNF-alpha expression by EPA is partly attributed to its inhibitory effect on NF-kappaB activation. EPA appears to prevent NF-kappaB activation by preventing the phosphorylation of IkappaB-alpha.

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