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Fecal Glucocorticoid Analysis: Non-invasive Adrenal Monitoring in Equids
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Published on: April 25, 2016

Glucocorticosteroids: current and future directions.

Peter J Barnes1

  • 1National Heart & Lung Institute, Imperial College, London, UK. p.j.barnes@imperial.ac.uk

British Journal of Pharmacology
|January 5, 2011
PubMed
Summary
This summary is machine-generated.

Glucocorticoids effectively treat asthma but not COPD due to resistance mechanisms. Oxidative stress reduces histone deacetylase-2, hindering anti-inflammatory actions and leading to glucocorticoid resistance.

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Area of Science:

  • Pharmacology
  • Molecular Biology
  • Immunology

Background:

  • Glucocorticoids are potent anti-inflammatory drugs for asthma.
  • Their efficacy is limited in chronic obstructive pulmonary disease (COPD).
  • Glucocorticoid action involves trans-repression and trans-activation of inflammatory and anti-inflammatory genes.

Purpose of the Study:

  • To elucidate the molecular mechanisms of glucocorticoid action and resistance.
  • To understand why glucocorticoids are less effective in COPD.
  • To explore potential therapeutic strategies for glucocorticoid resistance.

Main Methods:

  • Review of molecular mechanisms of glucocorticoid receptor (GR) function.
  • Analysis of gene transcription, histone acetylation, and mRNA stability.
  • Investigation of factors contributing to glucocorticoid resistance, including oxidative stress and histone deacetylase-2 (HDAC2) activity.

Main Results:

  • Glucocorticoids suppress inflammation by recruiting HDAC2 to inflammatory gene complexes (trans-repression).
  • At higher doses, they activate anti-inflammatory genes and genes causing side effects (trans-activation).
  • Glucocorticoid resistance in COPD and severe asthma is linked to reduced HDAC2 activity due to oxidative/nitrative stress.

Conclusions:

  • Glucocorticoid resistance is a significant clinical challenge, particularly in COPD.
  • Reduced HDAC2 activity is a key mechanism underlying this resistance.
  • Developing strategies to overcome glucocorticoid resistance and new anti-inflammatory treatments is crucial.