Changing ratios of omega-6 to omega-3 fatty acids can differentially modulate polychlorinated biphenyl toxicity in endothelial cells.
Exposure to persistent organic pollutants, such as polychlorinated biphenyls (PCBs) can cause endothelial cell (EC) activation by inducing pro-inflammatory signaling pathways. Our previous studies indicated that linoleic acid (LA, 18:2), a major omega-6 unsaturated fatty acid in the American diet, can potentiate PCB77-mediated inflammatory responses in EC. In addition, omega-3 fatty acids (such as alpha-linolenic acid, ALA and 18:3) are known for their anti-inflammatory properties. We tested the hypothesis that mechanisms of PCB-induced endothelial cell activation and inflammation can be modified by different ratios of omega-6 to omega-3 fatty acids. EC were pretreated with LA, ALA, or different ratios of these fatty acids, followed by exposure to PCB77. PCB77-induced oxidative stress and activation of the oxidative stress sensitive transcription factor nuclear factor kappaB (NF-kappaB) were markedly increased in the presence of LA and diminished by increasing the relative amount of ALA to LA. Similar protective effects by increasing ALA were observed by measuring NF-kappaB-responsive genes, such as vascular cell adhesion molecule-1 (VCAM-1) and cyclooxygenase-2 (COX-2). COX-2 catalyzes the rate limiting step of the biosynthesis of prostaglandin E(2) (PGE(2)). PCB77 exposure also increased PGE(2) levels, which were down-regulated with relative increasing amounts of ALA to LA. The present studies suggest that NF-kappaB is a critical player in the regulation of PCB-induced inflammatory markers as modulated by omega-6 and omega-3 fatty acids.
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D015232:Dinoprostone / Q000096:biosynthesis; D042783:Endothelial Cells / Q000187:drug effects* / Q000473:pathology*; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology*; D043371:Fatty Acids, Omega-6 / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D007249:Inflammation; D019787:Linoleic Acid / Q000494:pharmacology; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D011078:Polychlorinated Biphenyls / Q000633:toxicity*; D011651:Pulmonary Artery / Q000166:cytology; D013552:Swine; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D015525:Fatty Acids, Omega-3; D043371:Fatty Acids, Omega-6; D016328:NF-kappa B; D019010:Vascular Cell Adhesion Molecule-1; D019787:Linoleic Acid; D011078:Polychlorinated Biphenyls; D051546:Cyclooxygenase 2; D015232:Dinoprostone; C028451:3,4,3',4'-tetrachlorobiphenyl