Related Experiment Video

Updated: Jul 19, 2026

Generation of a Chronic Obstructive Pulmonary Disease Model in Mice by Repeated Ozone Exposure
08:17

Generation of a Chronic Obstructive Pulmonary Disease Model in Mice by Repeated Ozone Exposure

Published on: August 25, 2017

Corticosteroid resistance in chronic obstructive pulmonary disease: inactivation of histone deacetylase

Peter J Barnes1, Kazuhiro Ito, Ian M Adcock

  • 1Department of Thoracic Medicine, National Heart and Lung Institute, Imperial College, London SW3 6LY, UK. p.j.barnes@imperial.ac.uk

Lancet (London, England)
|March 6, 2004
PubMed

Insights

Patients with chronic obstructive pulmonary disease (COPD) show poor response to corticosteroids because smoking and oxidative stress impair histone deacetylase 2 (HDAC2). This suggests new therapies could overcome corticosteroid resistance in COPD.

Area of Science:

  • Molecular Biology
  • Pulmonary Medicine
  • Pharmacology

Background:

  • Corticosteroids are effective anti-inflammatory drugs for asthma but not for chronic obstructive pulmonary disease (COPD).
  • Inflammation in both diseases involves histone acetylation, which activates inflammatory genes.
  • Corticosteroids normally switch off gene transcription by recruiting histone deacetylase 2 (HDAC2).

Purpose of the Study:

  • To investigate the mechanism behind corticosteroid resistance in COPD.
  • To test the hypothesis that impaired HDAC2 function contributes to corticosteroid resistance in COPD.

Main Methods:

  • The study focuses on the molecular mechanisms of gene regulation in inflammatory diseases.
  • It examines the role of histone deacetylase 2 (HDAC2) in corticosteroid action.
  • The impact of oxidative stress and cigarette smoking on HDAC2 function is investigated.

Main Results:

  • In COPD patients, HDAC2 function is proposed to be impaired by cigarette smoking and oxidative stress.
  • Oxidative stress may impair HDAC2 via nitration, reducing its activity.
  • This impairment leads to reduced responsiveness to the anti-inflammatory effects of corticosteroids.

Conclusions:

  • Impaired HDAC2 function is a likely cause of corticosteroid resistance in COPD.
  • Therapeutic strategies targeting HDAC2 could potentially restore corticosteroid sensitivity.
  • This research opens avenues for novel anti-inflammatory treatments for COPD and other severe inflammatory conditions.

More Related Videos

A Mouse Model of Pulmonary Fibrosis Induced by Nasal Bleomycin Nebulization02:46

A Mouse Model of Pulmonary Fibrosis Induced by Nasal Bleomycin Nebulization

Published on: January 20, 2023

Refined Murine Model of Idiopathic Pulmonary Fibrosis07:51

Refined Murine Model of Idiopathic Pulmonary Fibrosis

Published on: June 17, 2025

Related Concept Videos

COPD: Pathogenesis and Clinical Features01:20

COPD: Pathogenesis and Clinical Features

Chronic obstructive pulmonary disease (COPD) is a group of lung conditions that progressively worsen over time, including chronic bronchitis and emphysema. This cluster of diseases collectively leads to a gradual and irreversible decline in lung function over time.
The primary cause for the onset of COPD is cigarette smoking and exposure to air pollution. These hazardous factors initiate a chain reaction within the lungs, resulting in chronic inflammation, damage to the airways, and a...
Chronic Obstructive Pulmonary Disease-II: Pathophysiology01:20

Chronic Obstructive Pulmonary Disease-II: Pathophysiology

Chronic Obstructive Pulmonary Disease (COPD) pathophysiology is intricate and multifaceted, involving a complex interplay of physiological processes. Understanding these mechanisms is crucial for effectively managing and treating COPD. Here is an in-depth look at the critical elements in the pathophysiology of COPD:
Chronic Inflammation
Chronic Obstructive Pulmonary Disease I: Introduction01:23

Chronic Obstructive Pulmonary Disease I: Introduction

Chronic obstructive pulmonary disease is a common, preventable, and treatable respiratory disorder characterized by persistent symptoms and progressive airflow limitation. This limitation results from a combination of small-airway disease (obstructive bronchiolitis) and parenchymal destruction (emphysema), both driven by chronic inflammation from exposure to harmful particles or gases.The disease includes two main pathological entities: emphysema, marked by destruction of alveolar walls and...
Chronic Obstructive Pulmonary Disease II: Emphysema01:23

Chronic Obstructive Pulmonary Disease II: Emphysema

Emphysema, a major phenotype of chronic obstructive pulmonary disease (COPD), is characterized by irreversible destruction of alveolar walls and permanent enlargement of distal airspaces. Unlike chronic bronchitis, which primarily affects the airways, emphysema predominantly involves the lung parenchyma, where structural damage leads to airflow limitation.PathophysiologyIt most commonly results from prolonged exposure to cigarette smoke and other toxic gases, particularly cigarette smoke.
Chronic Obstructive Pulmonary Disease III: Chronic Bronchitis Features01:24

Chronic Obstructive Pulmonary Disease III: Chronic Bronchitis Features

Chronic bronchitis is a key phenotype of chronic obstructive pulmonary disease (COPD), characterized by airway-centered inflammation and mucus overproduction. It develops from long-term exposure to harmful particles or gases, most commonly cigarette smoke, which triggers a persistent inflammatory response.Cellular and Structural ChangesInflammation initially affects the large bronchi and later the smaller airways, with infiltration by immune cells, including neutrophils, macrophages, and...
Chronic Pancreatitis II: Pathophysiology01:21

Chronic Pancreatitis II: Pathophysiology

Chronic pancreatitis is a progressive and irreversible inflammation of the pancreas, most often caused by long-term alcohol abuse, but it can also be related to ductal obstruction, smoking, or genetic factors.Chronic pancreatitis occurs when the pancreas is repeatedly exposed to harmful agents like alcohol, smoking, ductal obstruction, or genetic predisposition. These factors lead to the release of toxic metabolites and inflammatory cytokines, sustaining chronic inflammation in the pancreatic...