Abstract

Mast cells (MCs) play a key role in the development of allergic diseases. The interaction of antigens with immunoglobulin E and the subsequent binding of these complexes to the FcεRI receptor, which ultimately leads to rapid exocytosis of granules and subsequent production of cytokines, play a major role in MC activation in an allergy. There are data on the role of the mitochondrial membrane potential in the FcεRI-dependent activation of MCs. Thus, the use of classical uncouplers of oxidative phosphorylation reduces the level of MC degranulation. However, their effect on the production of MC cytokines has not been studied. In this work, it was demonstrated that pretreatment of RBL-2H3 MC with the uncoupler carbonyl cyanide-4-(trifluoromethoxy)phenylhydrazone (FCCP) leads to a decrease not only in the level of FcεRI-dependent degranulation but also in the production of TNFα and IL-4 cytokines. At the same time, FCCP prevents the phosphorylation of the LAT adapter molecule, as well as the Erk1/2 kinase, which may underlie the inhibitory effect of the uncoupler on the FcεRI-dependent activation of RBL-2H3 cell line. The data obtained indicate that the mitochondrial membrane potential plays an important role in the FcεRI-dependent activation of MCs, and the uncoupling of oxidative phosphorylation and respiration of mitochondria with the help of uncouplers can be used to regulate this process.

中文翻译：

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4-(三氟甲氧基)苯腙羰基氰化物 (FCCP) 对 RBL-2H3 细胞 FcεRI 依赖性细胞因子产生的影响

摘要

肥大细胞（MC）在过敏性疾病的发展中发挥着关键作用。抗原与免疫球蛋白 E 的相互作用以及随后这些复合物与 FcεRI 受体的结合，最终导致颗粒的快速胞吐作用和随后细胞因子的产生，在过敏中的 MC 激活中发挥着重要作用。有数据表明线粒体膜电位在 FcεRI 依赖性 MC 激活中的作用。因此，使用经典的氧化磷酸化解偶联剂可降低 MC 脱粒水平。然而，它们对 MC 细胞因子产生的影响尚未研究。在这项工作中，证明用解偶联剂羰基氰化物-4-(三氟甲氧基)苯腙 (FCCP) 预处理 RBL-2H3 MC 不仅会降低 FcεRI 依赖性脱粒水平，还会降低 TNFα 的产生和 IL-4 细胞因子。同时，FCCP 可防止 LAT 接头分子以及 Erk1/2 激酶的磷酸化，这可能是解偶联剂对 RBL-2H3 细胞系 FcεRI 依赖性激活的抑制作用的基础。获得的数据表明线粒体膜电位在MCs的FcεRI依赖性激活中起着重要作用，并且在解偶联剂的帮助下线粒体氧化磷酸化和呼吸的解偶联可用于调节这一过程。