Molecular Biology Reports

, Volume 40, Issue 6, pp 3995–4000

Expression level of histone deacetylase 2 correlates with occurring of chronic obstructive pulmonary diseases

  • Yiqing Qu
  • Yie Yang
  • Dedong Ma
  • Liangai He
  • Wei Xiao


Chronic obstructive pulmonary disease (COPD) is associated with chronic severe airway inflammation and causes increasing global health problems. New biological markers for COPD prediction and prognosis are urgently necessary. Previous studies indicate that histone deacetylases (HDACs) play essential roles in COPD. This study is to investigate if HDAC2 levels can be used as a promising, easily detected biomarker of COPD. In this paper, 49 COPD patients were enrolled and 42 healthy individuals (smokers or non-smokers) were used as healthy controls. Human bronchial epithelial cells derived from non-smokers, smokers, or COPD patients were grown in primary cultures. Total proteins were harvested from lung tissues or bronchial epithelial cells and then subjected to immunoblot analyses of HDAC2, HDAC3, and HDAC5. Quantitative RT-PCR analysis of HDAC2, HDAC3, and HDAC5 mRNA levels in tissues or cells were also preformed. We found that among the three HDAC proteins, the mRNA and protein levels of HDAC2, but not HDAC3 and HDAC5, in the tissues or cultured cells from patients have a significant correlation with development and prognosis of COPD. These results suggested that HDAC2 levels may serve as a promising, easily detected biomarker of COPD.


HDAC proteins COPD Biomarkers 


  1. 1.
    Barnes PJ (2000) Chronic obstructive pulmonary disease. New Engl J Med 343:269–280PubMedCrossRefGoogle Scholar
  2. 2.
    Rabe KF, Hurd S, Anzueto A et al (2007) Global strategy for the diagnosis, management, and prevention of COPD. Am J Respir Crit Care Med 176:532–555PubMedCrossRefGoogle Scholar
  3. 3.
    Barnes PJ (2007) Chronic obstructive pulmonary disease: a growing but neglected epidemic. PLoS Med 4:e112PubMedCrossRefGoogle Scholar
  4. 4.
    Grabiec AM, Tak PP, Reedquist KA (2011) Function of histone deacetylase inhibitors in inflammation. Crit Rev Immunol 31:233–263PubMedCrossRefGoogle Scholar
  5. 5.
    Kersul AL, Iglesias A, Ríos Á et al (2011) Molecular mechanisms of inflammation during exacerbations of chronic obstructive pulmonary disease. Arch Bronconeumol 47:176–183PubMedCrossRefGoogle Scholar
  6. 6.
    Urnov FD, Wolffe AP (2001) Chromatin remodeling and transcriptional activation: the cast (in order of appearance). Oncogene 20:2991–3006PubMedCrossRefGoogle Scholar
  7. 7.
    Blanchard F, Chipoy C (2005) Histone deacetylase inhibitors: new drugs for the treatment of inflammatory diseases? Drug Discov 10:197–204Google Scholar
  8. 8.
    Minucci S, Pelicci PG (2006) Histone deacetylase inhibitors and the promise of epigenetic (and more) treatments for cancer. Nat Rev Cancer 6:38–51PubMedCrossRefGoogle Scholar
  9. 9.
    Shakespear MR, Halili MA, Irvine KM, Fairlie DP, Sweet MJ (2011) Histone deacetylases as regulators of inflammation and immunity. Trends Immunol 32:335–343PubMedCrossRefGoogle Scholar
  10. 10.
    Vojinovic J, Damjanov N (2011) HDAC inhibition in rheumatoid arthritis and juvenile idiopathic arthritis. Mol Med 17:397–403PubMedCrossRefGoogle Scholar
  11. 11.
    Müller S, Krämer OH (2010) Inhibitors of HDACs–effective drugs against cancer? Curr Cancer Drug Targets 10:210–228PubMedCrossRefGoogle Scholar
  12. 12.
    Glozak MA, Sengupta N, Zhang X, Seto E (2005) Acetylation and deacetylation of non-histone proteins. Gene 363:15–23PubMedCrossRefGoogle Scholar
  13. 13.
    Li D, Marchenko ND, Moll UM (2011) SAHA shows preferential cytotoxicity in mutant p53 cancer cells by destabilizing mutant p53 through inhibition of the HDAC6-Hsp90 chaperone axis. Cell Death Differ 18:1904–1913PubMedCrossRefGoogle Scholar
  14. 14.
    Bansal N, Kadamb R, Mittal S, Vig L, Sharma R, Dwarakanath BS, Saluja D (2011) Tumor suppressor protein p53 recruits human Sin3B/HDAC1 complex for down-regulation of its target promoters in response to genotoxic stress. PLoS ONE 6:e26156PubMedCrossRefGoogle Scholar
  15. 15.
    Chen Y, Wang H, Yoon SO et al (2011) HDAC-mediated deacetylation of NF-κB is critical for Schwann cell myelination. Nat Neurosci 14:437–441PubMedCrossRefGoogle Scholar
  16. 16.
    Bendinelli P, Matteucci E, Maroni P, Desiderio MA (2009) NF-kappaB activation, dependent on acetylation/deacetylation, contributes to HIF-1 activity and migration of bone metastatic breast carcinoma cells. Mol Cancer Res 7:1328–1341PubMedCrossRefGoogle Scholar
  17. 17.
    Hsu YF, Sheu JR, Lin CH, Chen WC, Hsiao G, Ou G, Chiu PT, Hsu MJ (2011) MAPK phosphatase-1 contributes to trichostatin A inhibition of cyclooxygenase-2 expression in human umbilical vascular endothelial cells exposed to lipopolysaccharide. Biochim Biophys Acta 1810:1160–1169PubMedCrossRefGoogle Scholar
  18. 18.
    Hogg JC, Chu F, Utokaparch S et al (2004) The nature of smallairway obstruction in chronic obstructive pulmonary disease. New Engl J Med 350:2645–2653PubMedCrossRefGoogle Scholar
  19. 19.
    Ha MK, Song YH, Jeong SJ et al (2011) Emodin inhibits proinflammatory responses and inactivates histone deacetylase 1 in hypoxic rheumatoid synoviocytes. Biol Pharm Bull 34:1432–1437PubMedCrossRefGoogle Scholar
  20. 20.
    Patel IS, Roberts NJ, Lloyd-Owen SJ, Sapsford RJ, Wedzicha JA (2003) Airway epithelial inflammatory responses and clinical parameters in COPD. Eur Respir J 22:94–99PubMedCrossRefGoogle Scholar
  21. 21.
    Hogg JC (2004) Pathophysiology of airflow limitation in chronic obstructive pulmonary disease. Lancet 364:709–721PubMedCrossRefGoogle Scholar
  22. 22.
    Barnes PJ, Adcock IM, Ito K (2005) Histone acetylation and deacetylation: importance in inflammatory lung diseases. Eur Respir J 25:552–563PubMedCrossRefGoogle Scholar
  23. 23.
    de Ruijter AJ, van Gennip AH, Caron HN, Kemp S, van Kuilenburg AB (2003) Histone deacetylases (HDACs): characterization of the classical HDAC family. Biochem J 370:737–749PubMedCrossRefGoogle Scholar
  24. 24.
    Thiagalingam S, Cheng KH, Lee HJ, Mineva N, Thiagalingam A, Ponte JF (2003) Histone deacetylases: unique players in shaping the epigenetic histone code. Ann N Y Acad Sci 983:84–100PubMedCrossRefGoogle Scholar
  25. 25.
    Weerasinghe SV, Wambua M, Pflum MK (2010) A histone deacetylase-dependent screen in yeast. Bioorg Med Chem 18:7586–7592PubMedCrossRefGoogle Scholar
  26. 26.
    Ehrentraut S, Weber JM, Dybowski JN, Hoffmann D, Ehrenhofer-Murray AE (2010) Rpd3-dependent boundary formation at telomeres by removal of Sir2 substrate. Proc Natl Acad Sci U S A 107:5522–5527PubMedCrossRefGoogle Scholar
  27. 27.
    Yang XJ, Seto E (2008) The Rpd3/Hda1 family of lysine deacetylases: from bacteria and yeast to mice and men. Nat Rev Mol Cell Biol 9:206–218PubMedCrossRefGoogle Scholar
  28. 28.
    Choy JS, Acuña R, Au WC, Basrai MA (2011) A role for histone H4K16 hypoacetylation in Saccharomyces cerevisiae kinetochore function. Genetics 189:11–21PubMedCrossRefGoogle Scholar
  29. 29.
    Marwick JA, Kirkham PA, Stevenson CS et al (2004) Cigarette smoke alters chromatin remodelling and induces proinflammatory genes in rat lungs. Am J Respir Cell Mol Biol 31:633–642PubMedCrossRefGoogle Scholar
  30. 30.
    Ito K, Lim S, Caramori G, Chung KF, Barnes PJ, Adcock IM (2001) Cigarette smoking reduces histone deacetylase 2 expression, enhances cytokine expression and inhibits glucocorticoid actions in alveolar macrophages. FASEB J 15:1100–1102Google Scholar
  31. 31.
    Kim DR, Park MY, Lee CS et al (2011) Combination of vorinostat and adenovirus-TRAIL exhibits a synergistic antitumor effect by increasing transduction and transcription of TRAIL in lung cancer cells. Cancer Gene Ther 18:467–477PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2012

Authors and Affiliations

  • Yiqing Qu
    • 1
  • Yie Yang
    • 2
  • Dedong Ma
    • 1
  • Liangai He
    • 1
  • Wei Xiao
    • 1
  1. 1.Department of Respiratory MedicineQilu Hospital, Shandong UniversityJinanChina
  2. 2.Clinical Laboratory, Qianfoshan HospitalJinanChina

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