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 FcεRIα, β, and γ chains and phosphorylation of the γ 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 FcεRIα mRNA expression was determined by northern blot analysis. The protein level of FcεRI expressed on the plasma membrane was examined following IgE treatment by immunoprecipitation with anti-IgE light chain, followed by western blot analysis with anti-γ chain of FcR. Azelastine and epinastine had no effect on the FcεRIα, β and γ mRNA levels. Although the amount of γ chain assembled into IgE-bound FcεRI was not changed by treatment with azelastine nor epinastine, phosphorylation levels of γ chains of IgE-bound FcεRI were inhibited by azelastine. The inhibitory effect of azelastine on the IgE-mediated expression of FcεRIγ protein is not due to their inhibition of mRNA and protein expression, but due to abrogating phosphorylation of the γ chains, which is important for initiation of FcεRI signaling cascade elicited by IgE interaction.