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Effect of 4-(Trifluoromethoxy)phenylhydrazone Carbonyl Cyanide (FCCP) on FcεRI-Dependent Cytokine Production by RBL-2H3 Cells

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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.

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Funding

The work was supported by the Russian Science Foundation, project no. 22-74-00081.

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Authors and Affiliations

  1. Belozersky Institute of Physicochemical Biology, Moscow State University, 119992, Moscow, Russia

    A. N. Pavlyuchenkova, M. S. Smirnov & M. A. Chelombitko

  2. Faculty of Bioengineering and Bioinformatics, Moscow State University, 119992, Moscow, Russia

    A. N. Pavlyuchenkova & M. S. Smirnov

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  1. A. N. Pavlyuchenkova
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  2. M. S. Smirnov
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  3. M. A. Chelombitko
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Correspondence to M. A. Chelombitko.

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STATEMENT ON THE WELFARE OF ANIMALS

The study was conducted without the use of animals and without involving people as subjects.

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Translated by M. Shulskaya

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Pavlyuchenkova, A.N., Smirnov, M.S. & Chelombitko, M.A. Effect of 4-(Trifluoromethoxy)phenylhydrazone Carbonyl Cyanide (FCCP) on FcεRI-Dependent Cytokine Production by RBL-2H3 Cells. Moscow Univ. Biol.Sci. Bull. 78, 66–73 (2023). https://doi.org/10.3103/S0096392523020086

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