Inhibition of IgE-mediated phosphorylation of FcepsilonRIgamma 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 FcepsilonRIalpha, 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 FcepsilonRIalpha mRNA expression was determined by northern blot analysis. The protein level of FcepsilonRI 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 FcepsilonRIalpha, beta and gamma mRNA levels. Although the amount of gamma chain assembled into IgE-bound FcepsilonRI was not changed by treatment with azelastine nor epinastine, phosphorylation levels of gamma chains of IgE-bound FcepsilonRI were inhibited by azelastine. The inhibitory effect of azelastine on the IgE-mediated expression of FcepsilonRIgamma 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 FcepsilonRI signaling cascade elicited by IgE interaction.
Hanashiro
Kazuhiko
K
1st Department of Physiology, Unit of Physiological Science, School of Medicine, University of the Ryukyus, 207 Uehara, Nishihara, Okinawa 903-0215, Japan.
Sunagawa
Masanori
M
Nakasone
Toshiyuki
T
Nakamura
Mariko
M
Kosugi
Tadayoshi
T
D000818:Animals; D018926:Anti-Allergic Agents / Q000494:pharmacology*; D003984:Dibenzazepines / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology*; D007073:Immunoglobulin E / Q000378:metabolism*; D047468:Immunoprecipitation / Q000379:methods; D015471:Leukemia, Basophilic, Acute / Q000378:metabolism*; D008407:Mast Cells / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D010793:Phthalazines / Q000494:pharmacology*; D011485:Protein Binding; D051381:Rats; D017455:Receptors, IgE / Q000187:drug effects* / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism
D018926:Anti-Allergic Agents; D003984:Dibenzazepines; D007093:Imidazoles; D010793:Phthalazines; D017455:Receptors, IgE; D007073:Immunoglobulin E; D014443:Tyrosine; C053090:epinastine; C020976:azelastine