J Bacteriol Virol.  2009 Sep;39(3):205-216. 10.4167/jbv.2009.39.3.205.

Expression of Endothelin-1 by Stimulation with CXCL8 in Mouse Peritoneal Macrophages

Affiliations
  • 1Department of Obstetrics and Gynecology, College of Medicine, Yeungnam University, Daegu, Korea.
  • 2Department of Microbiology, College of Medicine, Yeungnam University, Daegu, Korea. heesun@med.yu.ac.kr
  • 3Department of Emergency Medicine, College of Medicine, Inha University, Incheon, Korea.

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.

Keyword

Endothelin-1; IL-8/CXCL8; Mouse peritoneal macrophages; 12-lipoxygenase

MeSH Terms

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
Arachidonate 12-Lipoxygenase
Endothelin-1
Flavanones
NF-kappa B
RNA, Messenger
RNA, Small Interfering
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