Coulombe Martin, Battistini Bruno, Stankova Jana, Pouliot Philippe, Bissonnette Elyse Y
Centre de Recherche, Hôpital Laval, Institut Universitaire de Cardiologie et de Pneumologie, Université Laval, 2725 Chemin Sainte-Foy, Sainte-Foy, Québec, Canada G1V 4G5.
J Leukoc Biol. 2002 May;71(5):829-36.
Mast 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 beta-hexosaminidase release and TNF, IL-4, IL-10, IL-12, IL-13, macrophage inflammatory protein-1alpha (MIP-1alpha), and nitric oxide (NO) production were investigated. ET-1 and -3 induced the release of beta-hexosaminidase and TNF and of mRNA expression. An antagonist of the ET(B) receptor subtype abrogated ET-stimulated TNF release, although ET(A) and ET(B) 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-1alpha 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.
肥大细胞已被证明可产生内皮素-1（ET-1）并表达ET受体。因此，我们推测ETs以自分泌方式调节肥大细胞介质的产生。将大鼠组织培养的肥大细胞（RCMC-1）与外源性ET-1或ET-3孵育，并研究β-己糖胺酶释放以及TNF、IL-4、IL-10、IL-12、IL-13、巨噬细胞炎性蛋白-1α（MIP-1α）和一氧化氮（NO）的产生。ET-1和ET-3诱导了β-己糖胺酶和TNF的释放以及mRNA表达。尽管通过免疫细胞化学已鉴定出ET(A)和ET(B)受体，但ET(B)受体亚型的拮抗剂消除了ET刺激的TNF释放。有趣的是，ET-1和ET-3抑制了Th2型细胞因子（IL-4、IL-10和IL-13）的mRNA表达（25%-30%），并增加了IL-12的释放（分别为39%和41%），而不影响MIP-1α和NO的产生。因此，我们的数据表明ETs可能通过调节肥大细胞产生的Th1/Th2细胞因子在调节细胞因子网络中发挥重要作用。
