Chapter 1. Molecular Mechanisms of Glucocorticoid Receptor Action

Summary

Glucocorticoids are the most effective therapy for the treatment of many chronic inflammatory diseases but they are ineffective in severe asthma and chronic obstructive pulmonary disease (COPD) for example. Glucocorticoids act by binding to and activating specific cytosolic receptors (GR). These receptors then translocate to the nucleus where they regulate gene expression. GR is able to selective repress specific inflammatory genes by differing actions on promoter-specific components of NF-κB and AP-1 activation complexes and also by effects on MAPK pathways. Importantly, these actions are mutually inhibitory. These pleitropic effects of GR may underlie there effectiveness in most patients with airways disease but suggests that abnormal activation of these pathways may result in glucocorticoid refractoriness. Understanding the molecular mechanisms of GR action may lead to the development of new anti-inflammatory drugs or enable clinicians to reverse the relative steroid-insensitivity that is characteristic of severe asthma and COPD for example.