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Histone deacetylase activity is decreased in peripheral blood monocytes in patients with COPD

DOI: 10.1186/1476-9255-9-10

Keywords: Chronic obstructive pulmonary disease, Histone deacetylase, Cigarette smoke, Inflammation

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Abstract:

HDAC 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.Compared 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.In 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.Chronic obstructive pulmonary disease (COPD) is not only an airway disease but also 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 [3-6]. 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 [7-10].Histone acetylase (HAT) and histone deacetylase (HDAC) are families of enzymes that regulate chromatin structure and inflammatory gene expression. Compared to healthy controls, COPD patients showed low HDAC activity in their alveolar macrophages [11,12]. This is believed to be associated with the

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