The effects of endothelin-1 on degranulation, cytokine and growth factor production by skin-derived mast cells.

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Endothelin-1 (ET-1), originally described as a vasoconstrictor, is now known to be involved in pathogenesis of various disorders including vascular, inflammatory, and fibrotic diseases. Recent studies suggest that mast cells are also involved in the same pathological conditions. In this study, we tested a hypothesis that ET-1 would affect mast cell functions and contribute to such disease conditions, using fetal skin-derived cultured mast cells (FSMC) and bone marrow-derived cultured cultured mast cells (BMMC). FSMC expressed ET receptors (ET_A and ET_B) at mRNA and protein levels, BMMC expressed lower levels of ET_A, and little, if any, ET_B. ET-1 induced degranulation by FSMC, but not by BMMC thorough ET_A-mediated pathways. ET-1 at different concentrations exerted the reciprocal effects on degranulation by IgE-bound FSMC. Furthermore, ET-1 induced TNFα and IL-6 production by FSMC, but not by BMMC, and significantly enhanced VEGF production and TGF-β1 mRNA expression by FSMC. Finally, ET-1 was produced by FSMC, but not by BMMC in response to Toll-like receptor ligands. These results indicate contrasting impacts of ET-1 on distinct mast cell populations. We propose that ET-1 may participate in pathological conditions of various disorders via its multi-functional effects on mast cells under certain conditions.