Endothelin-induced interleukin-6 production by rat aortic endothelial cells.
Endothelin (ET) produced by endothelial cells has recently been found to be a potent vasoconstricting hormone. In this paper, ET isopeptides, both ET-1 and ET-3, were shown to be potent stimulators of interleukin (IL)-6 production by a rat aortic endothelial cell clone, WAE-1. Semi-quantitative polymerase chain reaction analysis indicated that augmentation of IL-6 production is due to an increase in IL-6 messenger RNA level. Ligand binding assay indicated that most of the [125I]ET-1 binding sites correspond to ET receptor type A (ETAR). However, ET receptor type B (ETBR) was shown to be also present on this cell line by reverse transcription polymerase chain reaction using ETBR-specific primers and by ligand binding assay using [125I]ET-3, although the protein receptor level is much lower than that of ETAR. ET-1, but not ET-3, induced inositol 1,4,5-triphosphate production and an increase in intracellular Ca2+ concentration with similar dose response. These data suggest that ET-1 stimulates IL-6 production through ETAR-phospholipase C activation axis, whereas ET-3 stimulates IL-6 production through different signaling pathway. The results shown in this paper raise the possibility that ET plays a role in inducing inflammation in endothelium.
Xin
X
X
Institute for Animal Experimentation, University of Tokushima School of Medicine, Japan.
Cai
Y
Y
Matsumoto
K
K
Agui
T
T
D000818:Animals; D001011:Aorta / Q000166:cytology / Q000378:metabolism*; D001483:Base Sequence; D002460:Cell Line; D016232:Endothelins / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D015335:Molecular Probes / Q000235:genetics; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017466:Receptors, Endothelin / Q000235:genetics / Q000378:metabolism; D015290:Second Messenger Systems
D016232:Endothelins; D015850:Interleukin-6; D015335:Molecular Probes; D012333:RNA, Messenger; D017466:Receptors, Endothelin