Inhibition of IgE-mediated phosphorylation of FcεRIγ protein by antiallergic drugs in rat basophilic leukemia (RBL-2H3) cells:: A novel action of antiallergic drugs

We examined the effect of antiallergic drugs, azelastine and epinastine, on the expression of Fc epsilon RI alpha, beta, and gamma chains and phosphorylation of the gamma chains in rat basophilic leukemia (RBL-2H3) cells. The cells were cultured for 24 h with IgE treatment in the presence of azelastine or epinastine at the concentration of 10(-5) M. The Fc epsilon RI alpha mRNA expression was determined by northern blot analysis. The protein level of Fc epsilon RI expressed on the plasma membrane was examined following IgE treatment by immunoprecipitation with anti-IgE light chain, followed by western blot analysis with anti-gamma chain of FcR. Azelastine and epinastine had no effect on the Fc epsilon RI alpha, beta and gamma mRNA levels. Although the amount of gamma chain assembled into IgE-bound Fc epsilon RI was not changed by treatment with azelastine nor epinastine, phosphorylation levels of gamma chains of IgE-bound Fc epsilon RI were inhibited by azelastine. The inhibitory effect of azelastine on the IgE-mediated expression of Fc epsilon RI gamma protein is not due to their inhibition of mRNA and protein expression, but due to abrogating phosphorylation of the gamma chains, which is important for initiation of Fc epsilon RI signaling cascade elicited by IgE interaction. (c) 2007 Elsevier B.V. All rights reserved.