Role of histone deacetylase regulation in the pathogenesis of asthma in mice

Objective To compare the therapeutic effect of histone deacetylases(HDAC) inhibitor trichostatin A(TSA) and dexamethasone(Dex) in the treatment of asthmatic mouse model,so as to elucidate the role of histone deacetylase regulation in asthma pathogenesis.Methods Wild-type BALB/C mice were randomly divided into 4 groups,namely,the placebo group(group A),untreated asthma group(group B),Dex treated asthma group(group C) and TSA treated asthma group(group D).Animals in group B,C,D were sensitized intraperitoneally and challenged intranasally with ovalbumin.Group C was injected intraperitoneally with Dex(1.5 mg/kg,0.2 mL) and group D with TSA(1 mg/kg body weight,0.2 mL) 30 min before every challenge.Animals were then exsanguinated after the lung function examination.Blood and bronchoalveolar lavage fluid(BALF) and lung specimens were collected 24 h after the last challenge to assess the levels of interleukin(IL)-4 and interferon(IFN)-γ in the supernatants.The blood cell count and the count of white blood cell in the precipitate of BALF were measured;and the pathological change of the right upper lung tissue was observed.Results The asthmatic symptoms and high airway resistance in group C and D were significantly reduced and the lung dynamic compliance was significantly improved compared with group B(all P0.05).The counts of lymphocyte and eosinophil in the blood of group C were significantly lower than those of group B(P0.05 or 0.01).The counts of eosino-phil in BALF of group C and D were also lower than those of group B(P0.05).The count of eosinophils in the BALF of group D was lower than that of group C(P0.05).The concentrations of IL-4 in the BALF and blood of group C and D were significantly lower than those of group B(P0.01 or 0.05 respectively).The levels of IFN-γ were not significantly different between al the groups(P0.05).Conclusion Both TSA and Dex can release the asthmatic symptoms and improve high airway resistance and incompliance of lung.The inhibitory effect of TSA against proliferation of lymphocytes in BALF is weaker than that of Dex.Both Dex and TSA can decrease the concentrations of T helper cell type 2 cytokine IL-4 in BALF but can not increase IFN-γ.