Rationale: Chronic obstructive pulmonary disease (COPD) is believed to result from an abnormal inflammatory response in the lungs to noxious particles and gases usually found in cigarette smoke. VSports手机版.

Objectives: In this study, the molecular mechanisms for the enhanced proinflammatory cytokine gene transcription in COPD were investigated V体育安卓版. .

Methods: Lung tissue was examined from 56 subjects undergoing resection for peripheral lung tumors as follows: current smokers with (n = 14) and without COPD (n = 17), ex-smokers with COPD (n = 13), and nonsmokers (n = 12). The levels of inhibitor kappaB-alpha (IkappaB-alpha), histone deacetylase 2 (HDAC2), acetylated (ac-) histone H3 and H4, the transcription factor nuclear factor-kappaB (NF-kappaB), proinflammatory cytokine messenger RNA, and 8-isoprostane were measured V体育ios版. .

Measurements and main results: IkappaB-alpha levels were significantly decreased in healthy smokers and current and ex-smoking patients with COPD when compared with nonsmokers (p < 0. 001), with an associated increase in NF-kappaB DNA binding in current smokers (p < 0. 05). An increase in acetylated histone 4 (ac-H4; p < 0. 01) was found in current smokers. Conversely, ex-smokers with COPD showed an increase in ac-H3 (p < 0. 05). Decreased levels of cytoplasmic, but not nuclear, HDAC2 protein levels were detected. From the cytokine profiles, no significant differences were detected; however, interleukin-12p40 expression correlated with ac-H4 in current smokers with COPD (p < 0 VSports最新版本. 01). .

Conclusion: These data propose a role for modification of nucleosomal structure in inflammatory cytokine gene transcription in response to smoking V体育平台登录. The imbalance between histone deacetylation and acetylation in favor of acetylation may contribute to the enhanced inflammation in smokers susceptible to the development of COPD. .