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J Bacteriol Virol. 2009 Sep;39(3):205-216. Korean. Original Article.
Bae JJ , Kim JH , Kim H , Kim HS .
Department of Obstetrics and Gynecology, College of Medicine, Yeungnam University, Daegu, Korea.
Department of Microbiology, College of Medicine, Yeungnam University, Daegu, Korea.
Department of Emergency Medicine, College of Medicine, Inha University, Incheon, Korea.

Endothelin-1 (ET-1) has been characterized as a potent vasoconstrictor secreted by the endothelium, and play a major role in the regulation of vascular tone. It has been also known to participate in inflammatory reactions. The production of ET-1 by macrophages during infection and inflammation is related to tissue perfusion and leukocyte extravasation. The aim of this study is to investigate the role of IL-8/CXCL8, as a major inflammatory chemokine, for ET-1 expression in macrophges. Expression of ET-1 mRNA in mouse peritoneal macrophages (PeM phi) was weaker than that in vascular smooth muscle cells (VSMCs) from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). However, expression of IL-8/CXCL8-induced ET-1 mRNA in PeM phi was much more stronger than that in SHR and WKY VSMCs. Maximum expression of ET-1 mRNA was observed at 50 ng/ml dose of IL-8/CXCL8 and occurred at 2 h after addition of IL-8/CXCL8. Expression of ET-1 by IL-8/CXCL8 was dependent on NF-kappaB activation and ERK1/2 phosphorylation. Baicalein, a 12-lipoxygenase (LO) inhibitor, inhibited the expression of IL-8/CXCL8-induced ET-1 mRNA. This inhibitory action of baicalein was mediated via ERK1/2 inactivation. Induction of 12-LO mRNA by IL-8/CXCL8 and expression of ET-1 mRNA by 12-LO metabolite, 12(S)-HETE were also detected. The expression of IL-8/CXCL8-induced ET-1 mRNA was not detected in PeM phi transfected with 12-LO siRNA. These results suggest that IL-8/CXCL8 can act as one of main inducers of ET-1 in vascular inflammatory reactions, and ET-1 expression by IL-8/CXCL8 is related to 12-LO pathway in PeM phi.

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