Abstract
BackgroundHistone deacetylase (HDAC) is an enzyme that regulates chromatin structure and inflammatory gene expression. In patients with chronic obstructive pulmonary disease (COPD), while accumulating evidence indicates that the activity of HDAC is decreased in lung tissue alveolar macrophages, HDAC activity in peripheral inflammatory cells has not yet been evaluated in detail.MethodsHDAC activities in peripheral blood mononuclear cells (PBMC) were investigated in patients with stable COPD (n = 26), non-smoking controls (n = 13), and smoking controls (n = 10), respectively. HDAC activity was measured using an HDAC Activity/Inhibitor Screening Assay Kit. Serum interleukine-8 (CXCL8) levels were determined by ELISA techniques. Lung function test was carried out according to the ATS/ERS guidelines.ResultsCompared with healthy non-smokers, HDAC activity in the PBMCs of COPD patients was decreased by 40% (13.06 ± 5.95 vs. 21.39 ± 4.92 (μM/μg), p < 0.001). In patients with COPD, HDAC activity was negatively correlated to smoke intensity (r = -0.867, p < 0.001). In COPD patients who had smoked for more than 40 pack-years, HDAC activity in PBMC was 40% lower than that in COPD patients who had smoked fewer than 40 pack-years.Moreover, serum CXCL8 levels in patients with COPD were significantly higher than that in controls and were negatively correlated to HDAC activities.ConclusionIn patients with COPD, HDAC activity in the PBMCs is lower than that in healthy controls. The reduction of HDAC activity may be associated with smoking exposure through inflammatory pathways.
Highlights
Chronic obstructive pulmonary disease (COPD) is an airway disease and a systemic disorder that involves systemic inflammatory manifestations [1,2]
Histone deacetylase (HDAC) activity in peripheral blood mononuclear cells (PBMC) of chronic obstructive pulmonary disease (COPD) patients HDAC activity in the PBMCs of COPD patients was significantly decreased by 40% as compared to that in healthy non-smokers (13.06 ± 5.95 vs. 21.39 ± 4.92 μM/ μg, p < 0.001)
HDAC activity in PBMCs of healthy smokers was 40% lower than that observed in healthy non-smokers (12.50 ± 4.27 vs. 21.39 ± 4.92 μM/μg, p < 0.001). (Figure 1)
Summary
Chronic obstructive pulmonary disease (COPD) is an airway disease and a systemic disorder that involves systemic inflammatory manifestations [1,2]. In COPD, systemic inflammation is evidenced by increased levels of inflammatory cytokines in circulation even when the condition is stable [3,4,5,6]. Inflammatory cells such as macrophages and monocytes have been well known to be involved in pulmonary and systemic inflammation, but their exact role in the pathogenesis of COPD has not yet been clarified [7,8,9,10]. Histone deacetylase (HDAC) is an enzyme that regulates chromatin structure and inflammatory gene expression. In patients with chronic obstructive pulmonary disease (COPD), while accumulating evidence indicates that the activity of HDAC is decreased in lung tissue alveolar macrophages, HDAC activity in peripheral inflammatory cells has not yet been evaluated in detail
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