Eicosapentaenoic acid and docosahexaenoic acid modulate mitogen-activated protein kinase activity in endothelium.
Omega-3 polyunsaturated fatty acids (PUFA) regulate inflammation and immunoreaction partially via affecting endothelial functions. However, the intracellular signaling mechanisms for inhibiting endothelial activation by omega-3 PUFA remain unclear. We investigated the effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) on mitogen-activated protein kinases (MAPK) of endothelium. We analyzed the expression of extracellular signal-related kinases (ERK1/2), Jun amino-terminal kinases (JNK), and p38 mRNA by real-time RT-PCR and the kinases activity by western blotting in tumor necrosis factor-alpha (TNF-alpha)-activated human umbilical vein endothelial cells (HUVEC). We observed that EPA or DHA alone significantly reduced the TNF-alpha-induced activation of p38 and JNK kinases at a concentration of 20 microM, but EPA is a more potent inhibitor than DHA. In contrast, both EPA and DHA significantly counteracted the TNF-alpha-mediated deactivation of ERK1/2 kinases. Meanwhile, both EPA and DHA significantly attenuated the TNF-alpha-induced expression of p38 and ERK1/2 mRNA, and DHA but not EPA also reduced the TNF-alpha-induced JNK mRNA expression. We present data show that both EPA and DHA alone diminish activation of p38 and JNK kinases, while maintaining the activation of ERK1/2 kinases of TNF-alpha-stimulated HUVEC. This may contribute to the inhibiting effects of omega-3 PUFA on endothelial activation by proinflammatory stimuli.
Xue
Hua
H
Institute of General Surgery, Jinling Hospital, School of Medicine, Nanjing University, No. 305, East Zhongshan Road, Nanjing 210002, China.
Wan
Meifang
M
Song
Desheng
D
Li
Yousheng
Y
Li
Jieshou
J
D002478:Cells, Cultured; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D042783:Endothelial Cells / Q000187:drug effects* / Q000201:enzymology; D005786:Gene Expression Regulation; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism; D020935:MAP Kinase Signaling System; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid; D048031:JNK Mitogen-Activated Protein Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases