Eicosapentaenoic acid prevents lipopolysaccharide-stimulated DNA binding of activator protein-1 and c-Jun N-terminal kinase activity

Activator protein-1 (AP-1) is a transcription factor that plays an important role in regulating the expression of proinflammatory cytokines including tumor necrosis factor-α (TNF-α). Many studies have shown that fish oil supplementation inhibits TNF-α production in mice and humans; however, the mechanisms remain unclear. In this study, the effects of eicosapentaenoic acid (EPA), a major n-3 fatty acid in fish oil, on lipopolysaccharide (LPS)-stimulated activation of AP-1 were investigated in human monocytic THP-1 cells. The results demonstrated that AP-1 DNA binding activity stimulated by LPS was suppressed by preincubating cells with EPA. Lipopolysaccharide-stimulated increase of c-Jun and c-Fos protein levels was also attenuated by EPA pretreatment. In addition, EPA pretreatment decreased LPS-induced c-Jun phosphorylation and c-Jun N-terminal kinase (JNK) activation. The results suggest that suppression of TNF-α expression by EPA may be partly mediated by its inhibitory effect on AP-1 activation.