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 [I-125]ET-1 binding sites correspond to ET receptor type A (ET(A)R). However, ET receptor type B (ET(B)R) was shown to be also present on this cell Line by reverse transcription polymerase chain reaction using ET(B)R-specific primers and by ligand binding assay using [I-125]ET-3, although the protein receptor level is much lower than that of ET(A)R. 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 ET(A)R-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.