Antiallergic drugs, azelastine hydrochloride and epinastine hydrochloride, inhibit ongoing IgE secretion of rat IgE-producing hybridoma FE-3 cells.
Eur J Pharmacol
; 547(1-3): 174-83, 2006 Oct 10.
Article
em En
| MEDLINE
| ID: mdl-16925996
ABSTRACT
We asked whether or not antiallergic drugs, azelastine hydrochloride and epinastine hydrochloride, inhibit IgE secretion from IgE-producing hybridoma FE-3 cells. FE-3 cells were cultured in the presence of azelastine or epinastine for 24 h, washed in phosphate-buffered saline , and then recultured in the medium in the absence of the antiallergic drugs. IgE levels in the cultured medium as well as those in the cytoplasm of FE-3 cells were measured by enzyme-linked immunosorbent assay. mRNA levels of Cepsilon, activation-induced cytidine deaminase (AID), XBP-1, and Bip were estimated by northern blot or reverse transcriptase polymerase chain reaction analysis. The activities of nuclear factor-kappa B (NF-kappaB) were analyzed by electrophoretic mobility shift assay (EMSA). Phosphorylation of I kappa B alpha (IkappaBalpha) was analyzed by immunoprecipitation followed by western blot analysis. IgE levels in the cultured medium and in the microsome fraction were lower on the treatment with 10(-5) M azelastine or epinastine than those on the treatment with vehicle. Cepsilon and AID mRNA levels were lower on the treatment with 10(-5) M azelastine than those on the treatment with vehicle, but were not decreased on the treatment with 10(-5) M epinastine. XBP-1 and Bip mRNA levels were not altered following treatment of the antiallergic drugs. Azelastine at 10(-5) M, but not epinastine, reduced DNA binding activity of NF-kappaB and also diminished IkappaBalpha phosphorylation, leading to sustaining IkappaBalpha protein levels. These findings suggest that azelastine exerts its inhibitory effect on the IgE secretion from FE-3 cells through the inhibition of Cepsilon mRNA expression, and that the inhibitory effect of epinastine is, at least in part, due to suppression of IgE synthesis at the post-transcriptional level.
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Base de dados:
MEDLINE
Assunto principal:
Ftalazinas
/
Imunoglobulina E
/
Antialérgicos
/
Dibenzazepinas
/
Hibridomas
/
Imidazóis
Idioma:
En
Ano de publicação:
2006
Tipo de documento:
Article