Inhibition of airway inflammation and hyperresponsiveness by tetrandrine via downregulation of nuclear factor-κB and inducible nitric oxide synthase in asthmatic mice

Abstract

Objective To investigate the effect of tetrandrine(Tet) on the expression of nuclear factor-κB(NF-κB),inducible nitric oxide synthase(iNOS),airway inflammation and hyperresponsiveness in a murine model of bronchial asthma(asthma). Methods Thirty-two SPF BALB/c mice were randomly divided into 4 groups,including control group,asthma group,dexamethasone group(glucocorticoid group) and atetrandrine group(Tet group).Mice were sensitized and challenged by ovalbumin(OVA).Twentyfour hours after the last challenge,airway resistance was measured by pulmonary function detector. Hematoxylin& eosin(HE)staining was used to observe the airway inflammatory cells infiltration.Levels of total Ig E and OVA-specific IgE(OVA-sIgE) in serum and Th2 cytokines(IL-4 and IL-13) in bronchoalveolar lavage fluid(BALF) were detected by enzyme-linked immunosorbent assay(ELISA). Total number of inflammatory cells in BALF were counted with a microscope.Smears of BALF cells were stained with Wright's staining for eosinophils differential count.The protein expression of NF-κB and iNOS were determined by western blot analysis. Results Compared to the control group,the airway resistance,airway eosinophilia,total inflammatory cells and differential eosinophils count in BALF,total IgE and OVA-sIgE in serum,Th2 cytokines(IL-4 and IL-13)in BALF,as well as the protein expression of NF-κB and iNOS were significantly increased in asthma group(P< 0.05).In comparison with the asthma group,all the above indicators were remarkably decreased by treatment with either dexamethasone or tetrandrine(P< 0.05). Conclusions Tetrandrine may inhibit airway inflammation and hyperresponsiveness through downregulation of the expression of NF-κB and iNOS in asthmatic mice. Key words: Asthma; Tetrandrine; Nuclear factor-κB; Inducible nitric oxide synthase