Decreased Histone Deacetylase 2 (HDAC2) in Peripheral Blood Monocytes (PBMCs) of COPD Patients

Abstract

BackgroundHistone deacetylase 2 (HDAC2) is a class I histone deacetylase family member that plays a critical role in suppressing inflammatory gene expression in the airways, lung parenchyma, and alveolar macrophages in patients with chronic obstructive pulmonary disease (COPD). However, the expression of HDAC2 in peripheral blood monocytes (PBMCs), nuclear factor kappa B (NF-κB) p65, and serum inflammatory cytokine levels in COPD patients, smokers, and non-smokers remains unclear.MethodsPBMCs were obtained from COPD patients, healthy smokers, and healthy nonsmokers. The HDAC2 and NF-κB p65 expression were quantified by Western Blot. HDAC activity was assessed by an HDAC fluorometric immunoprecipitation activity assay kit. Serum tumor necrosis factor-alpha (TNF-α) and interleukin-8 (IL-8) levels were measured by ELISA.ResultsHDAC2 expression and HDAC activity were decreased in PBMCs in COPD patients compared with smokers and non-smokers. Increased NF-κB p65 expression, serum TNF-α and IL-8 levels were observed in COPD patients compared with nonsmokers. The FEV1%pred was positively correlated with HDAC2 expression and HDAC activity in COPD patients. Smokers had decreased HDAC activity, increased NF-κB p65 expression and serum TNF-α compared with nonsmokers.ConclusionsHDAC2 expression was decreased in PBMCs of COPD patients and was correlated with disease severity. The reduction of HDAC2 expression not only directly enhances the expression of inflammatory genes, but may account for the activation of NF-κB mediated inflammation. Decreased HDAC2 may serve as a potential biomarker of COPD and predict the decline of lung function.

Exercise-modulated epigenetic markers and inflammatory response in COPD individuals: A pilot study

“…In this sense, the phenotype of peripheral blood mononuclear cell (PBMC) is controlled through epigenetic signals that are involved in both activation and repression of specific genes involved in the immune response as well as in the production of inflammatory mediators (Shanmugam and Sethi, 2013). Regarding COPD, previous work demonstrated altered levels of histone deacetylase (HDAC) in immune cells from patients compared to matched controls (Tan et al, 2016;To et al, 2012). Interestingly, the histone hyperacetylation status in PBMC of COPD patients was also accompanied by higher expression of NF-κB and increased systemic levels of TNF-α and IL-8 (Ito et al, 2005).…”

LncRNA HOXA‐AS2 positively regulates osteogenesis of mesenchymal stem cells through inactivating NF‐κB signalling

“…Increasing evidence revealed NF-κB is involved in the deacetylase HDAC2-mediated histone H3 lysine 27 acetylation (H3K27ac). 33,34 Therefore, we suspected HOXA-AS2 may regulate the SP7 expression in a NF-κB-mediate HDAC2 acetylation manner.…”

Targeting Transcription Factor Lysine Acetylation in Inflammatory Airway Diseases

“…The nuclear factor kappa-lightchain-enhancer of activated B cells (NF-κB) transcription factor plays an important role in this. Upregulated NF-κB activity has been reported in asthma [57] and COPD [51,58]. NF-κB is subject to regulation by lysine acetylations [59].…”

“…In more recent studies, decreased HDAC2 expression was also found in PBMCs and lymphocytes in COPD [50,51]. In COPD, the decreased HDAC2 expression and activity can be linked to glucocorticoid resistance [52].…”