TY - JOUR
T1 - Cardiotrophin-1 stimulates endothelin-1 via gp130 in vascular endothelial cells
AU - Jougasaki, Michihisa
AU - Larsen, Amy M.
AU - Cataliotti, Alessandro
AU - Christiansen, David C.
AU - Burnett, John C.
N1 - Funding Information:
We thank Denise M. Heublein, Sharon M. Sandberg and Gail J. Harty for excellent assistance. This work was supported by grants from American Heart Association of the Minnesota Affiliate (MN-97-GB-06), the National Institute of Health (HL 36634), the Miami Heart Research Institute, the Bruce and Ruth Rappaport Program in Vascular Biology, and Mayo Foundation.
PY - 2002/8
Y1 - 2002/8
N2 - 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.
AB - 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.
KW - Endothelium
KW - Hormone
KW - Immunocytochemistry
KW - Peptides
KW - Radioimmunoassay
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U2 - 10.1016/S0196-9781(02)00078-5
DO - 10.1016/S0196-9781(02)00078-5
M3 - Article
C2 - 12182945
AN - SCOPUS:0036701495
SN - 0196-9781
VL - 23
SP - 1441
EP - 1447
JO - Peptides
JF - Peptides
IS - 8
ER -