New Insights into the Molecular Mechanisms of Corticosteroids Actions

Author(s): Ian M. Adcock, Gaetano Caramori, Kazuhiro Ito.

Journal Name: Current Drug Targets

Volume 7 , Issue 6 , 2006

Become EABM
Become Reviewer

Abstract:

Corticosteroids produce a marked improvement in clinical parameters in most asthmatic patients; in contrast, corticosteroids have little effect on lung function measurements in patients with chronic obstructive pulmonary disease. By uncovering the reason for this paradox, it should be possible to implement treatment regimens that restore corticosteroid sensitivity. Corticosteroids exert their effects by binding to a cytoplasmic receptor, which is subjected to posttranslational modifications. Receptor phosphorylation may influence hormone binding and nuclear translocation, alter glucocorticoid receptor interactions and protein half-life. Other modifications such as nitration/nitrosylation may also affect glucocorticoid receptor function. Oxidative stress due to cigarette smoke may be a mechanism for the corticosteroid resistance observed in chronic obstructive pulmonary disease, as it enhances proinflammatory transcription and reduces glucocorticoid receptor-associated repressor functions. Therapies targeting these aspects of the glucocorticoid receptor activation pathway may reverse steroid resistance in patients with chronic obstructive pulmonary disease.

Keywords: Inflammation, COPD, Oxidative stress, Steroid resistance, Dissociated steroids

Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 7
ISSUE: 6
Year: 2006
Page: [649 - 660]
Pages: 12
DOI: 10.2174/138945006777435344
Price: $65

Article Metrics

PDF: 8

Special-new-year-discount