Effect of Autophagy Regulators on FcεRI-Dependent Activation of the RBL-2H3 Cells

Abstract

Mast cells (MCs) are an important population of connective tissue cells that play a key role in the development of allergic diseases. The main pathway of MC activation in allergies is associated with the interaction of antigen complexes with immunoglobulin E and their subsequent binding to the FcεRI receptor. This leads to rapid release of secretory granules and cytokine production. In recent years, there has been increasing evidence for the involvement of autophagy in many processes, including MC function. Therefore, autophagy regulators can be used as potential inhibitors of MC activity and as therapeutic agents for the treatment of allergic diseases. In the present study, we investigated the effects of two autophagy inhibitors SBI-0206965 and LY294002, and one autophagy activator rapamycin on FcεRI-dependent activation of RBL-2H3, which usually used as model of MCs and basophils. Cell activation was assessed by determining the content of the secretory granule marker β-hexosaminidase and the levels of the cytokines TNF, IL-4 and IL-13. Treatment of cells with SBI-0206965 and LY294002 was shown to reduce FcεRI-dependent degranulation and IL-4 cytokine secretion by RBL-2H3 cells, while the use of rapamycin resulted in reduction of the level of IL-13 cytokine. This indicates the prospect of potential application of these autophagy regulators in the therapy of allergic diseases.