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

内皮素-1 （ET-1）最初被描述为一种血管收缩剂，现在已知参与多种疾病的发病机制，包括血管、炎症和纤维化疾病。最近的研究表明肥大细胞也参与了相同的病理状况。在本研究中，我们使用胎儿皮肤来源的培养肥大细胞（FSMC）和骨髓来源的培养肥大细胞（BMMC）验证了ET-1会影响肥大细胞功能并导致此类疾病的假设。FSMC在mRNA和蛋白水平上表达ET受体（ET_A和ET_B）， BMMC表达较低水平的ET_A和很少（如果有的话）ET_B。ET-1通过FSMC诱导脱颗粒，而不是通过et_a介导的BMMC。不同浓度的ET-1对ige结合的FSMC的脱粒有互反作用。此外，ET-1诱导FSMC产生TNFα和IL-6，而BMMC不产生TNFα和IL-6，并显著提高FSMC产生VEGF和TGF-β1 mRNA的表达。最后，ET-1是由FSMC产生的，而不是由BMMC响应toll样受体配体产生的。这些结果表明ET-1对不同肥大细胞群的不同影响。我们认为ET-1可能在一定条件下通过对肥大细胞的多功能作用参与多种疾病的病理过程。

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.