[Background] It has been known that 5-10% of asthmatic patients are resistant to the steroid therapy. However, mechanisms underlying the acquisition of steroid resistance have been unclear. GRs consist of two alternatively spliced isoforms: GRα, which activates gene transcription, and GRβ, a dominant-negative receptor. Objective of this study is to elucidate whether mRNA levels of GRα and GRβ in eosinophils are increased in steroid-resistant asthma mice.   
[Methods] Ovalbumin (OVA)-sensitized BALB/c mice were intratracheally challenged with OVA at 5 or 500 µg/animal 4 times. Dexamethasone (1 mg/kg) was i.p. administered during the multiple challenges. One day after the 4th challenge, eosinophils in the lung were purified by FACS. mRNA levels of GRα and GRβ in the eosinophils were quantified by real-time RT-PCR. Airway remodeling was evaluated by staining with PAS and Masson trichrome. 
[Results]  (1)　Infiltration of eosinophils and development of airway remodeling in 5 µg OVA model were suppressed by dexamethasone, whereas those in 500 µg OVA model were not. (2) GRβ mRNA level in eosinophils from 500 µg OVA model was higher than that from 5 µg OVA model. No difference in GRα mRNA level was detected between the two models.
[Conclusion] The increased expression of GRβ may account for the acquisition of steroid resistance.