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.