Endothelins regulate mediator production of rat tissue-cultured mucosal mast cells. Up-regulation of Th1 and inhibition of Th2 cytokines

Abstract

AbstractMast cells have been shown to produce endothelin-1 (ET-1) and to express ET receptors. Thus, we postulated that ETs modulate mast cell mediator production in an autocrine manner. Rat tissue-cultured mast cells (RCMC-1) were incubated with exogenous ET-1 or ET-3, and β-hexosaminidase release and TNF, IL-4, IL-10, IL-12, IL-13, macrophage inflammatory protein-1α (MIP-1α), and nitric oxide (NO) production were investigated. ET-1 and -3 induced the release of β-hexosaminidase and TNF and of mRNA expression. An antagonist of the ETB receptor subtype abrogated ET-stimulated TNF release, although ETA and ETB receptors have been identified by immunocytochemistry. It is interesting that ET-1 and ET-3 inhibited (25–30%) mRNA expression of Th2-type cytokines (IL-4, IL-10, and IL-13) and increased IL-12 release (39% and 41%, respectively) without affecting MIP-1α and NO production. Thus, our data suggest that ETs may play an important role in modulating the cytokine network by regulating Th1/Th2 cytokine production by mast cells.