Expression of Endothelin-1 by Stimulation with CXCL8 in Mouse Peritoneal Macrophages.
10.4167/jbv.2009.39.3.205
- Author:
Jei Jun BAE
1
;
Jung Hae KIM
;
Hoon KIM
;
Hee Sun KIM
Author Information
1. Department of Obstetrics and Gynecology, College of Medicine, Yeungnam University, Daegu, Korea.
- Publication Type:Original Article
- Keywords:
Endothelin-1;
IL-8/CXCL8;
Mouse peritoneal macrophages;
12-lipoxygenase
- MeSH:
Animals;
Arachidonate 12-Lipoxygenase;
Endothelin-1;
Endothelium;
Flavanones;
Inflammation;
Leukocytes;
Macrophages;
Macrophages, Peritoneal;
Mice;
Muscle, Smooth, Vascular;
NF-kappa B;
Perfusion;
Phosphorylation;
Rats;
Rats, Inbred SHR;
RNA, Messenger;
RNA, Small Interfering
- From:Journal of Bacteriology and Virology
2009;39(3):205-216
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
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.
