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Current Drug Targets

Editor-in-Chief

ISSN (Print): 1389-4501
ISSN (Online): 1873-5592

New Insights into the Molecular Mechanisms of Corticosteroids Actions

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

Volume 7, Issue 6, 2006

Page: [649 - 660] Pages: 12

DOI: 10.2174/138945006777435344

Price: $65

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


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