EFFECT OF 4-(TRIFLUOROMETHOXY)PHENYLHYDRAZONE CARBONYL CYANIDE (FCCP) ON FCΕRI-DEPENDENT CYTOKINE PRODUCTION BY RBL-2H3 CELLS

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 allergy. There is data on the role of the mitochondrial membrane potential in the FcεRI-dependent activation of MC. Thus, the use of classical uncouplers of oxidative phosphorylation reduces MC degranulation. However, their e ect on the production of MC cytokines has not been studied. In the present work, it was demonstrated that pretreatment of RBL-2H3 mast cells with the uncoupler carbonyl cyanide-4-(tri uoromethoxy)phenylhydrazone (FCCP) leads to a decrease not only in FcεRI-dependent degranulation, but also in a decrease 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 e ect of the uncoupler on 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 MC, and the uncoupling of oxidative phosphorylation and respiration of mitochondria with the help of uncouplers can be used to regulate this process.