Effects of beclomethasone and carbocysteine in histone acetylation/deacetylation processes of bronchial epithelial cells exposed to cigarette smoke

Histone deacetylase expression/activity may control inflammation, cell senescence and responses to corticosteroids. Cigarette smoke exposure, increasing oxidative stress, may negatively affect deacetylase expression/activity. The effects of cigarette smoke extracts (CSE), carbocysteine and beclomethasone on chromatin remodelling processes in human bronchial epithelial cells are largely unknown. The present study was aimed to assess the effects of cigarette smoke, carbocysteine and beclomethasone on histone deacetylase 3 (HDAC3)expression/activity, histone acetyltransferases expression (HAT), pCREB and IL-1 m-RNA expression, neutrophil chemotaxis and p53 protein expression. CSE decreased HDAC3 expression and activity and m-RNA expression of N-CoR (nuclear receptor corepressor). At the same time, CSE increased the expression of the HAT, p300. All these events increased acetylation within the cells thus contributing to increased pCREB expression, IL-1 m-RNA expression, neutrophil chemotaxis and p53 protein expression. The incubation of CSE exposed cells with carbocysteine and beclomethasone counteracted the effects of cigarette smoke on HDAC3 , N-CoR and p300. The increased deacetylation processes due to carbocysteine and beclomethasone incubation is associated to reduced pCREB, IL-1 m-RNA expression, neutrophil chemotaxis and p53 protein expression. These findings suggest a new role of combination therapy with beclomethasone and carbocysteine in restoring deacetylation processes compromised by cigarette smoke exposure.