Related Experiment Videos
Cardiotrophin-1 stimulates endothelin-1 via gp130 in vascular endothelial cells
Michihisa Jougasaki1, Amy M Larsen, Alessandro Cataliotti
1Institute for Clinical Research, National Hospital Kyushu Cardiovascular Center, 8-1 Shiroyama-cho, Kagoshima 892-0853, Japan. michi@qjun.hosp.go.jp
Insights
Cardiotrophin-1 (CT-1) and glycoprotein 130 (gp130) are present in canine aortic endothelial cells. CT-1 stimulates endothelin-1 (ET-1) secretion via the gp130 system.
Area of Science:
- Vascular Biology
- Endocrinology
- Cytokine Signaling
Background:
- Endothelin-1 (ET-1) is a peptide released by endothelial cells, regulating vascular tone and proliferation.
- Cytokines, such as interleukin-6, stimulate ET-1 synthesis and secretion.
- Cardiotrophin-1 (CT-1) is an interleukin-6-type cytokine that signals through glycoprotein 130 (gp130).
Purpose of the Study:
- To determine the presence and role of the CT-1/gp130 system in vascular endothelial cells.
- To investigate if CT-1 stimulates ET-1 synthesis and secretion in these cells.
Main Methods:
- Cultured canine aortic endothelial cells (CAECs) were used.
- Gene expression was analyzed using Northern blot.
- Protein localization was assessed via immunocytochemistry.
- ET-1 secretion was measured, and gp130 function was inhibited using a monoclonal antibody.
Main Results:
- CT-1, gp130, and ET-1 were detected in CAECs.
- CT-1 significantly increased ET-1 gene expression and secretion in a dose-dependent manner.
- Inhibition of gp130 attenuated CT-1-induced ET-1 secretion, indicating mediation through the gp130 receptor system.
Conclusions:
- Vascular endothelial cells express the CT-1/gp130 cytokine system.
- CT-1 stimulates ET-1 secretion in endothelial cells through the gp130 receptor pathway.
- This study elucidates a novel mechanism for regulating ET-1 secretion involving CT-1 and gp130.
Abstract:
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.