Effects of Carbocysteine and Beclomethasone on Histone Acetylation/Deacetylation Processes in Cigarette Smoke Exposed Bronchial Epithelial Cells

Histone deacetylase expression/activity may control inflammation, cell senescence, and responses to corticosteroids. Cigarette smokeexposure, increasing oxidative stress, may negatively affect deacetylase expression/activity. The effects of cigarette smoke extracts (CSE),carbocysteine, and beclomethasone dipropionate on chromatin remodeling processes in human bronchial epithelial cells are largelyunknown. The present study was aimed to assess the effects of cigarette smoke, carbocysteine, and beclomethasone dipropionate onhistone deacetylase 3 (HDAC3) expression/activity, N-CoR (nuclear receptor corepressor) expression, histone acetyltransferases (HAT)(p300/CBP) expression, p-CREB and IL-1 m-RNA expression, neutrophil chemotaxis. Increased p-CREB expression was observed in thebronchial epithelium of smokers. CSE increased p-CREB expression and decreased HDAC3 expression and activity and N-CoR m-RNAand protein expression. At the same time, CSE increased the expression of the HAT, p300/CBP. All these events increased acetylationprocesses within the cells and were associated to increased IL-1 m-RNA expression and neutrophil chemotaxis. The incubation of CSEexposed cells with carbocysteine and beclomethasone counteracted the effects of cigarette smoke on HDAC3 and N-CoR but not onp300/CBP. The increased deacetylation processes due to carbocysteine and beclomethasone dipropionate incubation is associated toreduced p-CREB, IL-1 m-RNA expression, neutrophil chemotaxis. These findings suggest a new role of combination therapy withcarbocysteine and beclomethasone dipropionate in restoring deacetylation processes compromised by cigarette smoke exposure.