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Original Research |
Expression by Preventing NF-
B Activation
Graduate Center for Nutritional Sciences (Y.Z., L.H.C.), Internal Medicine (S.J.-B., S.B.), University of Kentucky, Lexington, KY
Address reprint requests to: Dr. Linda Chen, Graduate Center for Nutritional Sciences, 204 Funkhouser Building, University of Kentucky, Lexington, KY 40506-0054. Phone: (859) 257-3288. E-mail: lchen{at}uky.edu
Background: Many studies have shown that fish oil supplementation inhibits tumor necrosis factor-
(TNF-) production in mice and human subjects; however, the mechanisms remain unclear. Nuclear factor-
B (NF-B) is a transcription factor that plays an important role in controlling the expression of pro-inflammatory genes including TNF-. Activation of NF-B has been shown to mediate the maximal expression of TNF- in human monocytes. NF-B is kept in an inactive form in the cytoplasm by IB, the inhibitory subunit of NF-B complex. Phosphorylation and subsequent degradation of IB lead to NF-B 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- and activation of NF-B were investigated. The mechanism underlying EPA modulation of NF-B activation was also studied.
Methods: Human monocytic THP-1 cells were pre-incubated with EPA and stimulated with LPS. The levels of secreted TNF- were determined by ELISA. The DNA binding activity of NF-B was analyzed by EMSA. The degradation and phosphorylation of IB- were examined by Western blot analysis.
Results: TNF- production and expression induced by LPS were significantly decreased in cells pre-incubated with EPA. LPS-induced NF-B activation, translocation of p65 subunit to the nucleus, phosphorylation and degradation of IB- were partially prevented by EPA.
Conclusions: The results suggest that suppression of the TNF- expression by EPA is partly attributed to its inhibitory effect on NF-B activation. EPA appears to prevent NF-B activation by preventing the phosphorylation of IB-.
Key words: eicosapentaenoic acid, fish oil, LPS, TNF-, NF-B, IB-
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