Cardiotrophin-1 stimulates endothelin-1 via gp130 in vascular endothelial cells.
Endothelin-1 (ET-1) is a vasoconstricting and mitogenic peptide released from vascular endothelial cells under normal and pathophysiological conditions, and synthesis and secretion of ET-1 are stimulated by cytokines. Cardiotrophin-1 (CT-1) is a new member of the interleukin-6-type cytokines that induce biological actions through the glycoprotein (gp) 130. The present study was designed to determine the presence of CT-1 and the gp130 cytokine system in vascular endothelial cells and to investigate whether CT-1 stimulates synthesis and secretion of ET-1 in the vascular endothelial cells. We first sought to determine gene expression and immunoreactivity of CT-1, gp130 and ET-1 in cultured canine aortic endothelial cells (CAECs) using Northern blot analysis and immunocytochemistry, which revealed the presence of CT-1 and gp130 together with ET-1 in CAECs. CT-1 increased ET-1 gene expression in CAECs, and stimulated ET-1 secretion from CAECs in a dose-dependent manner. Furthermore, inhibition of gp130 by monoclonal antibody attenuated ET-1 secretion from CAECs, suggesting that actions of CT-1 on the secretion of ET-1 are mediated through gp130 receptor system. The present study, therefore, reports the presence of CT-1 and gp130 in vascular endothelial cells and mechanisms of secretion of ET-1 related to this cytokine system.
Institute for Clinical Research, National Hospital Kyushu Cardiovascular Center, 8-1 Shiroyama-cho, Kagoshima 892-0853, Japan. michi@qjun.hosp.go.jp
Michihisa
M
Jougasaki
Amy M
AM
Larsen
Alessandro
A
Cataliotti
David C
DC
Christiansen
John C
JC
Burnett
D000818:Animals; D000906:Antibodies / Q000276:immunology; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D001013:Aorta, Thoracic / Q000276:immunology / Q000378:metabolism; D015152:Blotting, Northern; D050822:Cytokine Receptor gp130; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D004285:Dogs; D019332:Endothelin-1 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000276:immunology / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
D000906:Antibodies; D015703:Antigens, CD; D016207:Cytokines; D019332:Endothelin-1; D008562:Membrane Glycoproteins; D050822:Cytokine Receptor gp130; C092073:cardiotrophin 1