help button home button
AJRCCM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ito, K.
Right arrow Articles by Adcock, I. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ito, K.
Right arrow Articles by Adcock, I. M.
American Journal of Respiratory and Critical Care Medicine Vol 166. pp. 392-396, (2002)
© 2002 American Thoracic Society

Original Article

Expression and Activity of Histone Deacetylases in Human Asthmatic Airways

Kazuhiro Ito, Gaetano Caramori, Sam Lim, Tim Oates, K. Fan Chung, Peter J. Barnes and Ian M. Adcock

Thoracic Medicine, National Heart and Lung Institute, Imperial College School of Medicine, London, United Kingdom

Correspondence and requests for reprints should be addressed to Dr. Ian M. Adcock, Ph.D., Thoracic Medicine, National Heart and Lung Institute, Imperial College School of Medicine, Dovehouse Street, London, SW3 6LY United Kingdom. E-mail: ian.adcock{at}ic.ac.uk

Asthma is a chronic inflammatory disease that is characterized by increased expression of multiple inflammatory genes. Chromatin modification plays a critical role in the regulation of these genes. Acetyaltion of histones by histone acetyltransferases (HATs) is associated with increased gene transcription, whereas hypocetylation induced by histone deacetylases (HDACs) is associated with suppression of gene expression. We have examined the expression and activity of HATs and HDACs in bronchial biopsies from normal subjects and subjects with asthma. There was no difference in the site of HDAC1–HDAC6 expression between normal subjects and subjects with asthma, but subjects with asthma had reduced HDAC enzymatic activity and reduced HDAC1 and HDAC2 protein expression, as measured by Western blotting. In contrast, subjects with asthma treated with inhaled steroids were found to have greater HDAC activity than untreated subjects with asthma, although still lower than control subjects. In contrast, although there was no change in the site of HAT (CREB binding protein and p300/CREB binding protein–associated factor) expression, HAT activity was increased in subjects with asthma. HAT activity was reduced to control levels in subjects with asthma treated with inhaled steroids. The increase in HAT activity and reduced HDAC activity in asthma may underlie the increased expression of multiple inflammatory genes, and this is reversed, at least in part, by treatment with inhaled steroids.

Key Words: asthma • histone acetylation • histone deacetylase activity • gene expression




This article has been cited by other articles:


Home page
 Ther Adv Respir DisHome page
P. J. Barnes
Histone deacetylase-2 and airway disease
Therapeutic Advances in Respiratory Disease, October 1, 2009; 3(5): 235 - 243.
[Abstract] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
T. R. Bartling and M. L. Drumm
Loss of CFTR results in reduction of histone deacetylase 2 in airway epithelial cells
Am J Physiol Lung Cell Mol Physiol, July 1, 2009; 297(1): L35 - L43.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
D. Adenuga, H. Yao, T. H. March, J. Seagrave, and I. Rahman
Histone Deacetylase 2 Is Phosphorylated, Ubiquitinated, and Degraded by Cigarette Smoke
Am. J. Respir. Cell Mol. Biol., April 1, 2009; 40(4): 464 - 473.
[Abstract] [Full Text] [PDF]

Home page
 Eur Heart JHome page
D. Pons, F. R. de Vries, P. J. van den Elsen, B. T. Heijmans, P. H.A. Quax, and J. W. Jukema
Epigenetic histone acetylation modifiers in vascular remodelling: new targets for therapy in cardiovascular disease
Eur. Heart J., February 1, 2009; 30(3): 266 - 277.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
T. R. Bartling and M. L. Drumm
Oxidative Stress Causes IL8 Promoter Hyperacetylation in Cystic Fibrosis Airway Cell Models
Am. J. Respir. Cell Mol. Biol., January 1, 2009; 40(1): 58 - 65.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
K. Ito, C. Herbert, J. S. Siegle, C. Vuppusetty, N. Hansbro, P. S. Thomas, P. S. Foster, P. J. Barnes, and R. K. Kumar
Steroid-Resistant Neutrophilic Inflammation in a Mouse Model of an Acute Exacerbation of Asthma
Am. J. Respir. Cell Mol. Biol., November 1, 2008; 39(5): 543 - 550.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
R. L. Miller and S.-m. Ho
Environmental Epigenetics and Asthma: Current Concepts and Call for Studies
Am. J. Respir. Crit. Care Med., March 15, 2008; 177(6): 567 - 573.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
D. Cao, P. A. Bromberg, and J. M. Samet
COX-2 Expression Induced by Diesel Particles Involves Chromatin Modification and Degradation of HDAC1
Am. J. Respir. Cell Mol. Biol., August 1, 2007; 37(2): 232 - 239.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
The American Lung Association Asthma Clinical Rese
Clinical Trial of Low-Dose Theophylline and Montelukast in Patients with Poorly Controlled Asthma
Am. J. Respir. Crit. Care Med., February 1, 2007; 175(3): 235 - 242.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
S. Keslacy, O. Tliba, H. Baidouri, and Y. Amrani
Inhibition of Tumor Necrosis Factor-{alpha}-Inducible Inflammatory Genes by Interferon-{gamma} Is Associated with Altered Nuclear Factor-{kappa}B Transactivation and Enhanced Histone Deacetylase Activity
Mol. Pharmacol., February 1, 2007; 71(2): 609 - 618.
[Abstract] [Full Text] [PDF]

Home page
 Eur Respir JHome page
E. Livingston, R. Chaudhuri, A. D. McMahon, I. Fraser, C. P. McSharry, and N. C. Thomson
Systemic sensitivity to corticosteroids in smokers with asthma
Eur. Respir. J., January 1, 2007; 29(1): 64 - 71.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
M. Hew, P. Bhavsar, A. Torrego, S. Meah, N. Khorasani, P. J. Barnes, I. Adcock, K. Fan Chung, and for the National Heart Lung and Blood Institute's
Relative Corticosteroid Insensitivity of Peripheral Blood Mononuclear Cells in Severe Asthma
Am. J. Respir. Crit. Care Med., July 15, 2006; 174(2): 134 - 141.
[Abstract] [Full Text] [PDF]

Home page
 Eur Respir JHome page
P. J. Barnes
Corticosteroid effects on cell signalling
Eur. Respir. J., February 1, 2006; 27(2): 413 - 426.
[Abstract] [Full Text] [PDF]

Home page
 Proc Am Thorac SocHome page
P. J. Barnes
Theophylline in Chronic Obstructive Pulmonary Disease: New Horizons
Proceedings of the ATS, November 1, 2005; 2(4): 334 - 339.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
S. Wenzel
Severe Asthma in Adults
Am. J. Respir. Crit. Care Med., July 15, 2005; 172(2): 149 - 160.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
M. Nie, A. J. Knox, and L. Pang
{beta}2-Adrenoceptor Agonists, Like Glucocorticoids, Repress Eotaxin Gene Transcription by Selective Inhibition of Histone H4 Acetylation
J. Immunol., July 1, 2005; 175(1): 478 - 486.
[Abstract] [Full Text] [PDF]

Home page
 NEJMHome page
K. Ito, M. Ito, W. M. Elliott, B. Cosio, G. Caramori, O. M. Kon, A. Barczyk, S. Hayashi, I. M. Adcock, J. C. Hogg, et al.
Decreased Histone Deacetylase Activity in Chronic Obstructive Pulmonary Disease
N. Engl. J. Med., May 12, 2005; 352(19): 1967 - 1976.
[Abstract] [Full Text] [PDF]

Home page
 Eur Respir JHome page
P. J. Barnes, I. M. Adcock, and K. Ito
Histone acetylation and deacetylation: importance in inflammatory lung diseases
Eur. Respir. J., March 1, 2005; 25(3): 552 - 563.
[Abstract] [Full Text] [PDF]

Home page
 Eur Respir JHome page
N.C. Thomson, R. Chaudhuri, and E. Livingston
Asthma and cigarette smoking
Eur. Respir. J., November 1, 2004; 24(5): 822 - 833.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
B. G. Cosio, B. Mann, K. Ito, E. Jazrawi, P. J. Barnes, K. F. Chung, and I. M. Adcock
Histone Acetylase and Deacetylase Activity in Alveolar Macrophages and Blood Mononocytes in Asthma
Am. J. Respir. Crit. Care Med., July 15, 2004; 170(2): 141 - 147.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
R. Chaudhuri, E. Livingston, A. D. McMahon, L. Thomson, W. Borland, and N. C. Thomson
Cigarette Smoking Impairs the Therapeutic Response to Oral Corticosteroids in Chronic Asthma
Am. J. Respir. Crit. Care Med., December 1, 2003; 168(11): 1308 - 1311.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
S. E. Wenzel, H. W. Chu, P. Silkoff, S. O'Sullivan, L. Poulter, M. Akveld, and C. M. Burke
Ensuring Quality in Pharmaceutical Studies
Am. J. Respir. Crit. Care Med., October 15, 2003; 168(8): 1010 - 1012.
[Full Text]

Home page
 ANN INTERN MEDHome page
P. J. Barnes and I. M. Adcock
How Do Corticosteroids Work in Asthma?
Ann Intern Med, September 2, 2003; 139(5_Part_1): 359 - 370.
[Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
P. J. Barnes
Theophylline: New Perspectives for an Old Drug
Am. J. Respir. Crit. Care Med., March 15, 2003; 167(6): 813 - 818.
[Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
M. J. Tobin
Asthma, Airway Biology, and Nasal Disorders in AJRCCM 2002
Am. J. Respir. Crit. Care Med., February 1, 2003; 167(3): 319 - 332.
[Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
P. J. Sterk and L. Koenderman
Transcriptional Machinery in Asthma: Closing the Gap with Clinical Phenotypes
Am. J. Respir. Crit. Care Med., August 1, 2002; 166(3): 260 - 261.
[Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Proc. Am. Thorac. Soc. Am. J. Respir. Cell Mol. Biol.
Copyright © 2002 American Thoracic Society 		  CCM abstracts