INTRACELLULAR SIGNAL TRANSDUCTION FOR INTERLEUKIN-1-BETA-INDUCED ENDOTHELIN PRODUCTION IN HUMAN UMBILICAL VEIN ENDOTHELIAL-CELLS

The authors investigated the intracellular signal transduction for interleukin (IL)-1β-induced endothelin (ET) production by endothelial cells from cultured human umbilical vein (HUVEC). Cultured HUVEC released immunoreactive.(iR)-ET into the media in a time-dependent manner and a significant increase of iR-ET production was observed by the addition of IL-1β. The stimulating effect of IL-1β on iR-ET production was respectively inhibited by protein kinase C (C kinase) inhibitor (H-7), Ca-calmodulin inhibitor (W-7), cyclic AMP-dependent protein kinase (A kinase) inhibitor (H-8) and tyrosine kinase inhibitor (genistain) in a dose-dependent fashion. The data suggested that intracellular signal transduction for IL-1β-induced iR-ET production were via such pathways as C kinase, A kinase, Ca-calmodulin and tyrosine kinase in combination or independently, though possible mediation by other pathways cannot be ruled out. © 1992.