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Published in: Journal of Inflammation 1/2012

Open Access 01-12-2012 | Research

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

Authors: Yanwei Chen, Ping Huang, Wen Ai, Xiaoli Li, Wei Guo, Jingnong Zhang, Jiong Yang

Published in: Journal of Inflammation | Issue 1/2012

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Abstract

Background

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.

Methods

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.

Results

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.

Conclusion

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.
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Literature
1.
go back to reference Rabe KF, Hurd S, Anzueto A, Barnes PJ, Buist SA, Calverley P, Fukuchi Y, Jenkins C, Rodriguez-Roisin R, van Weel C, Zielinski J: Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med. 2007, 176: 532-555. 10.1164/rccm.200703-456SO.CrossRefPubMed Rabe KF, Hurd S, Anzueto A, Barnes PJ, Buist SA, Calverley P, Fukuchi Y, Jenkins C, Rodriguez-Roisin R, van Weel C, Zielinski J: Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J Respir Crit Care Med. 2007, 176: 532-555. 10.1164/rccm.200703-456SO.CrossRefPubMed
2.
go back to reference Fabbri LM, Rabe KF: From COPD to chronic systemic inflammatory syndrome?. Lancet. 2007, 370: 797-799. 10.1016/S0140-6736(07)61383-X.CrossRefPubMed Fabbri LM, Rabe KF: From COPD to chronic systemic inflammatory syndrome?. Lancet. 2007, 370: 797-799. 10.1016/S0140-6736(07)61383-X.CrossRefPubMed
3.
go back to reference Aaron SD, Vandemheen KL, Ramsay T, Zhang C, Avnur Z, Nikolcheva T, Quinn A: Multi analyte profiling and variability of inflammatory markers in blood and induced sputum in patients with stable COPD. Respir Res. 2010, 11: 41-10.1186/1465-9921-11-41.PubMedCentralCrossRefPubMed Aaron SD, Vandemheen KL, Ramsay T, Zhang C, Avnur Z, Nikolcheva T, Quinn A: Multi analyte profiling and variability of inflammatory markers in blood and induced sputum in patients with stable COPD. Respir Res. 2010, 11: 41-10.1186/1465-9921-11-41.PubMedCentralCrossRefPubMed
4.
go back to reference Dentener MA, Creutzberg EC, Schols AM, Mantovani A, van't Veer C, Buurman WA, Wouters EF: Systemic anti-inflammatory mediators in COPD: increase in soluble interleukin 1 receptor II during treatment of exacerbations. Thorax. 2001, 56: 721-726. 10.1136/thorax.56.9.721.PubMedCentralCrossRefPubMed Dentener MA, Creutzberg EC, Schols AM, Mantovani A, van't Veer C, Buurman WA, Wouters EF: Systemic anti-inflammatory mediators in COPD: increase in soluble interleukin 1 receptor II during treatment of exacerbations. Thorax. 2001, 56: 721-726. 10.1136/thorax.56.9.721.PubMedCentralCrossRefPubMed
5.
go back to reference Mannino DM, Ford ES, Redd SC: Obstructive and restrictive lung disease and markers of inflammation: data from the Third National Health and Nutrition Examination. Am J Med. 2003, 114: 758-762. 10.1016/S0002-9343(03)00185-2.CrossRefPubMed Mannino DM, Ford ES, Redd SC: Obstructive and restrictive lung disease and markers of inflammation: data from the Third National Health and Nutrition Examination. Am J Med. 2003, 114: 758-762. 10.1016/S0002-9343(03)00185-2.CrossRefPubMed
6.
go back to reference Petersen AM, Penkowa M, Iversen M, Frydelund-Larsen L, Andersen JL, Mortensen J, Lange P, Pedersen BK: Elevated levels of IL-18 in plasma and skeletal muscle in chronic obstructive pulmonary disease. Lung. 2007, 185: 161-171. 10.1007/s00408-007-9000-7.CrossRefPubMed Petersen AM, Penkowa M, Iversen M, Frydelund-Larsen L, Andersen JL, Mortensen J, Lange P, Pedersen BK: Elevated levels of IL-18 in plasma and skeletal muscle in chronic obstructive pulmonary disease. Lung. 2007, 185: 161-171. 10.1007/s00408-007-9000-7.CrossRefPubMed
7.
go back to reference Becker S, Soukup JM, Gallagher JE: Differential particulate air pollution induced oxidant stress in human granulocytes, monocytes and alveolar macrophages. Toxicol In Vitro. 2002, 16: 209-218. 10.1016/S0887-2333(02)00015-2.CrossRefPubMed Becker S, Soukup JM, Gallagher JE: Differential particulate air pollution induced oxidant stress in human granulocytes, monocytes and alveolar macrophages. Toxicol In Vitro. 2002, 16: 209-218. 10.1016/S0887-2333(02)00015-2.CrossRefPubMed
8.
go back to reference Tetley TD: Macrophages and the pathogenesis of COPD. Chest. 2002, 121: 156S-159S. 10.1378/chest.121.5_suppl.156S.CrossRefPubMed Tetley TD: Macrophages and the pathogenesis of COPD. Chest. 2002, 121: 156S-159S. 10.1378/chest.121.5_suppl.156S.CrossRefPubMed
9.
go back to reference Barnes PJ: Alveolar macrophages as orchestrators of COPD. Copd. 2004, 1: 59-70. 10.1081/COPD-120028701.CrossRefPubMed Barnes PJ: Alveolar macrophages as orchestrators of COPD. Copd. 2004, 1: 59-70. 10.1081/COPD-120028701.CrossRefPubMed
10.
go back to reference Pons AR, Noguera A, Blanquer D, Sauleda J, Pons J, Agusti AG: Phenotypic characterisation of alveolar macrophages and peripheral blood monocytes in COPD. Eur Respir J. 2005, 25: 647-652. 10.1183/09031936.05.00062304.CrossRefPubMed Pons AR, Noguera A, Blanquer D, Sauleda J, Pons J, Agusti AG: Phenotypic characterisation of alveolar macrophages and peripheral blood monocytes in COPD. Eur Respir J. 2005, 25: 647-652. 10.1183/09031936.05.00062304.CrossRefPubMed
11.
go back to reference Barnes PJ: Role of HDAC2 in the pathophysiology of COPD. Annu Rev Physiol. 2009, 71: 451-464. 10.1146/annurev.physiol.010908.163257.CrossRefPubMed Barnes PJ: Role of HDAC2 in the pathophysiology of COPD. Annu Rev Physiol. 2009, 71: 451-464. 10.1146/annurev.physiol.010908.163257.CrossRefPubMed
12.
go back to reference Ito K, Ito M, Elliott WM, Cosio B, Caramori G, Kon OM, Barczyk A, Hayashi S, Adcock IM, Hogg JC, Barnes PJ: Decreased histone deacetylase activity in chronic obstructive pulmonary disease. N Engl J Med. 2005, 352: 1967-1976. 10.1056/NEJMoa041892.CrossRefPubMed Ito K, Ito M, Elliott WM, Cosio B, Caramori G, Kon OM, Barczyk A, Hayashi S, Adcock IM, Hogg JC, Barnes PJ: Decreased histone deacetylase activity in chronic obstructive pulmonary disease. N Engl J Med. 2005, 352: 1967-1976. 10.1056/NEJMoa041892.CrossRefPubMed
13.
go back to reference Sarir H, Mortaz E, Janse WT, Givi ME, Nijkamp FP, Folkerts G: IL-8 production by macrophages is synergistically enhanced when cigarette smoke is combined with TNF-alpha. Biochem Pharmacol. 2010, 79: 698-705. 10.1016/j.bcp.2009.10.001.CrossRefPubMed Sarir H, Mortaz E, Janse WT, Givi ME, Nijkamp FP, Folkerts G: IL-8 production by macrophages is synergistically enhanced when cigarette smoke is combined with TNF-alpha. Biochem Pharmacol. 2010, 79: 698-705. 10.1016/j.bcp.2009.10.001.CrossRefPubMed
14.
go back to reference Mortaz E, Lazar Z, Koenderman L, Kraneveld AD, Nijkamp FP, Folkerts G: Cigarette smoke attenuates the production of cytokines by human plasmacytoid dendritic cells and enhances the release of IL-8 in response to TLR-9 stimulation. Respir Res. 2009, 10: 47-10.1186/1465-9921-10-47.PubMedCentralCrossRefPubMed Mortaz E, Lazar Z, Koenderman L, Kraneveld AD, Nijkamp FP, Folkerts G: Cigarette smoke attenuates the production of cytokines by human plasmacytoid dendritic cells and enhances the release of IL-8 in response to TLR-9 stimulation. Respir Res. 2009, 10: 47-10.1186/1465-9921-10-47.PubMedCentralCrossRefPubMed
15.
go back to reference Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, Crapo R, Enright P, van der Grinten CP, Gustafsson P, et al: Standardisation of spirometry. Eur Respir J. 2005, 26: 319-338. 10.1183/09031936.05.00034805.CrossRefPubMed Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, Crapo R, Enright P, van der Grinten CP, Gustafsson P, et al: Standardisation of spirometry. Eur Respir J. 2005, 26: 319-338. 10.1183/09031936.05.00034805.CrossRefPubMed
16.
go back to reference Cosio BG, Mann B, Ito K, Jazrawi E, Barnes PJ, Chung KF, Adcock IM: Histone acetylase and deacetylase activity in alveolar macrophages and blood mononocytes in asthma. Am J Respir Crit Care Med. 2004, 170: 141-147. 10.1164/rccm.200305-659OC.CrossRefPubMed Cosio BG, Mann B, Ito K, Jazrawi E, Barnes PJ, Chung KF, Adcock IM: Histone acetylase and deacetylase activity in alveolar macrophages and blood mononocytes in asthma. Am J Respir Crit Care Med. 2004, 170: 141-147. 10.1164/rccm.200305-659OC.CrossRefPubMed
17.
go back to reference Ito K, Lim S, Caramori G, Cosio B, Chung KF, Adcock IM, Barnes PJ: A molecular mechanism of action of theophylline: Induction of histone deacetylase activity to decrease inflammatory gene expression. Proc Natl Acad Sci USA. 2002, 99: 8921-8926. 10.1073/pnas.132556899.PubMedCentralCrossRefPubMed Ito K, Lim S, Caramori G, Cosio B, Chung KF, Adcock IM, Barnes PJ: A molecular mechanism of action of theophylline: Induction of histone deacetylase activity to decrease inflammatory gene expression. Proc Natl Acad Sci USA. 2002, 99: 8921-8926. 10.1073/pnas.132556899.PubMedCentralCrossRefPubMed
18.
go back to reference Chung KF, Adcock IM: Multifaceted mechanisms in COPD: inflammation, immunity, and tissue repair and destruction. Eur Respir J. 2008, 31: 1334-1356. 10.1183/09031936.00018908.CrossRefPubMed Chung KF, Adcock IM: Multifaceted mechanisms in COPD: inflammation, immunity, and tissue repair and destruction. Eur Respir J. 2008, 31: 1334-1356. 10.1183/09031936.00018908.CrossRefPubMed
19.
go back to reference van Eeden SF, Sin DD: Chronic obstructive pulmonary disease: a chronic systemic inflammatory disease. Respiration. 2008, 75: 224-238. 10.1159/000111820.CrossRefPubMed van Eeden SF, Sin DD: Chronic obstructive pulmonary disease: a chronic systemic inflammatory disease. Respiration. 2008, 75: 224-238. 10.1159/000111820.CrossRefPubMed
20.
go back to reference Kim V, Rogers TJ, Criner GJ: New concepts in the pathobiology of chronic obstructive pulmonary disease. Proc Am Thorac Soc. 2008, 5: 478-485. 10.1513/pats.200802-014ET.PubMedCentralCrossRefPubMed Kim V, Rogers TJ, Criner GJ: New concepts in the pathobiology of chronic obstructive pulmonary disease. Proc Am Thorac Soc. 2008, 5: 478-485. 10.1513/pats.200802-014ET.PubMedCentralCrossRefPubMed
21.
go back to reference Sevenoaks MJ, Stockley RA: Chronic Obstructive Pulmonary Disease, inflammation and co-morbidity-a common inflammatory phenotype?. Respir Res. 2006, 7: 70-10.1186/1465-9921-7-70.PubMedCentralCrossRefPubMed Sevenoaks MJ, Stockley RA: Chronic Obstructive Pulmonary Disease, inflammation and co-morbidity-a common inflammatory phenotype?. Respir Res. 2006, 7: 70-10.1186/1465-9921-7-70.PubMedCentralCrossRefPubMed
22.
go back to reference Miller M, Cho JY, Pham A, Friedman PJ, Ramsdell J, Broide DH: Persistent airway inflammation and emphysema progression on CT in ex-smokers observed for 4 years. Chest. 2011, 139 (6): 1380-7. 10.1378/chest.10-0705.PubMedCentralCrossRefPubMed Miller M, Cho JY, Pham A, Friedman PJ, Ramsdell J, Broide DH: Persistent airway inflammation and emphysema progression on CT in ex-smokers observed for 4 years. Chest. 2011, 139 (6): 1380-7. 10.1378/chest.10-0705.PubMedCentralCrossRefPubMed
23.
go back to reference Willemse BW, ten Hacken NH, Rutgers B, Lesman-Leegte IG, Postma DS, Timens W: Effect of 1-year smoking cessation on airway inflammation in COPD and asymptomatic smokers. Eur Respir J. 2005, 26: 835-845. 10.1183/09031936.05.00108904.CrossRefPubMed Willemse BW, ten Hacken NH, Rutgers B, Lesman-Leegte IG, Postma DS, Timens W: Effect of 1-year smoking cessation on airway inflammation in COPD and asymptomatic smokers. Eur Respir J. 2005, 26: 835-845. 10.1183/09031936.05.00108904.CrossRefPubMed
24.
go back to reference Lapperre TS, Postma DS, Gosman MM, Snoeck-Stroband JB, ten Hacken NH, Hiemstra PS, Timens W, Sterk PJ, Mauad T: Relation between duration of smoking cessation and bronchial inflammation in COPD. Thorax. 2006, 61: 115-121. 10.1136/thx.2005.040519.PubMedCentralCrossRefPubMed Lapperre TS, Postma DS, Gosman MM, Snoeck-Stroband JB, ten Hacken NH, Hiemstra PS, Timens W, Sterk PJ, Mauad T: Relation between duration of smoking cessation and bronchial inflammation in COPD. Thorax. 2006, 61: 115-121. 10.1136/thx.2005.040519.PubMedCentralCrossRefPubMed
25.
go back to reference Garcia-Rio F, Miravitlles M, Soriano JB, Munoz L, Duran-Tauleria E, Sanchez G, Sobradillo V, Ancochea J: Systemic inflammation in chronic obstructive pulmonary disease: a population-based study. Respir Res. 2010, 11: 63-PubMedCentralCrossRefPubMed Garcia-Rio F, Miravitlles M, Soriano JB, Munoz L, Duran-Tauleria E, Sanchez G, Sobradillo V, Ancochea J: Systemic inflammation in chronic obstructive pulmonary disease: a population-based study. Respir Res. 2010, 11: 63-PubMedCentralCrossRefPubMed
Metadata
Title
Histone deacetylase activity is decreased in peripheral blood monocytes in patients with COPD
Authors
Yanwei Chen
Ping Huang
Wen Ai
Xiaoli Li
Wei Guo
Jingnong Zhang
Jiong Yang
Publication date
01-12-2012
Publisher
BioMed Central
Published in
Journal of Inflammation / Issue 1/2012
Electronic ISSN: 1476-9255
DOI
https://doi.org/10.1186/1476-9255-9-10

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