Arginine vasopressin attenuates the effects of TNF-α in aortic endothelial cells by inducing ectodomain shedding of TNF receptor 1.
Biochem Biophys Res Commun
; 511(4): 780-786, 2019 04 16.
Article
in En
| MEDLINE
| ID: mdl-30833075
ABSTRACT
In septic shock, arginine vasopressin (AVP) is commonly used as a vasopressor to restore blood pressure. Exogenous AVP may have anti-inflammatory effects as well. We investigated whether AVP modulates the effects of tumor necrosis factor-α (TNF-α) in human aortic endothelial cells (HAECs). TNF-α stimulated intercellular adhesion molecule-1 expression, while AVP pretreatment attenuated this effect of TNF-α. Upon treatment with AVP, extracellular Ca2+ entered the cells rapidly through L-type calcium channels, which in turn induced cell surface translocation of a disintegrin and metalloprotease 10 (ADAM10) and ectodomain shedding of tumor necrosis factor receptor 1 (TNFR1). On the other hand, siRNA depletion of ADAM10 suppressed AVP-induced ectodomain shedding of TNFR1 and eliminated the inhibitory effect of AVP against TNF-α. Depletion of oxytocin receptor also abolished AVP-induced extracellular Ca2+ influx, AVP-induced ectodomain shedding of TNFR1 and the inhibitory effect of AVP against TNF-α. These findings suggest that AVP decreases the responsiveness of HAECs to TNF-α by inducing ADAM10-dependent ectodomain shedding of TNFR1. Extracellular Ca2+ influx through L-type calcium channels was essential for ADAM10 activation. This effect of AVP was mediated through the oxytocin receptor.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Vasoconstrictor Agents
/
Arginine Vasopressin
/
Tumor Necrosis Factor-alpha
/
Endothelial Cells
/
Receptors, Tumor Necrosis Factor, Type I
Limits:
Humans
Language:
En
Journal:
Biochem Biophys Res Commun
Year:
2019
Document type:
Article