title: Eicosapentaenoic acid prevents lipopolysaccharide-stimulated DNA binding of activator protein-1 and c-Jun N-terminal kinase activity.
abstract: 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-alpha (TNF-alpha). Many studies have shown that fish oil supplementation inhibits TNF-alpha 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-alpha expression by EPA may be partly mediated by its inhibitory effect on AP-1 activation.
authors.affiliation: Graduate Center for Nutritional Sciences, University of Kentucky, Lexington, KY 40506, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Linda H
authors.initials: LH
authors.lastname: Chen
mesh_terms: D002460:Cell Line; D004247:DNA / Q000378:metabolism*; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000378:metabolism*
chemical_list: D008070:Lipopolysaccharides; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1; D004247:DNA; D015118:Eicosapentaenoic Acid; D048031:JNK Mitogen-Activated Protein Kinases