Cigarette smoking reduces histone deacetylase 2 expression, enhances cytokine expression, and inhibits glucocorticoid actions in alveolar macrophages

Abstract

SPECIFIC AIMSGlucocorticoidsact, at least in part, through recruitment of histone deacetylases (HDACs) to sites of inflammatory gene transcription. In this study we show that cigarette smoke, an oxidative stress, decreased HDAC activity in human biopsies and macrophages in vivo. This reduced activity correlated with enhanced induction of inflammatory cytokines and a reduction in glucocorticoid responsiveness in vitro.PRINCIPAL FINDINGS1. HAT and HDAC expression in bronchial biopsies and alveolar macrophages.The histone acetyltransferases (HATs) CBP and HDAC1 and HDAC2 are localized within the airway to all cells with the most intense staining within the epithelium and inflammatory cells. Smoking did not affect the site of the expression of any of these proteins. Western blot analysis detected no difference in the expression of CBP or PCAF between the two groups. In contrast, there was a decrease in HDAC2 expression (0.63±0.02 vs. 0.37±0.06 OD units, P<0.01), but not HDAC1 (0.55±0.07 versus 0.55±0.10 OD un...