Post-transcriptional and nongenomic effects of glucocorticoids.
The ability of glucocorticoids to interfere with post-transcriptional gene regulation has recently been recognized as a potentially important part of their anti-inflammatory property, and the mechanisms governing such activity are under active investigation. Several studies have shown that glucocorticoids can inhibit inflammatory signaling pathways known to control mRNA turnover and translation. Moreover, several glucocorticoid-sensitive determinants have been identified on mRNA molecules of inflammatory genes, and the RNA-binding factors interacting with them might constitute relevant glucocorticoid targets. Glucocorticoids also exert effects characterized as nongenomic, which occur within minutes of drug administration. The mechanisms of action of nongenomic glucocorticoid effects differ from the classical, transcription-dependent glucocorticoid action and involve the production of second-messenger molecules and activation of signal transduction pathways, either by the nuclear glucocorticoid receptor or by a membrane glucocorticoid receptor that has not yet been fully characterized. Ultimately, the discovery of novel pathways involved in mediating the actions of glucocorticoids should lead to improved targets for anti-inflammatory therapy.
Stellato
Cristiana
C
Johns Hopkins Asthma and Allergy Center, 5501 Hopkins Bayview Circle, Room 1A.12A, Baltimore, MD 21224, USA. stellato@jhmi.edu
D005786:Gene Expression Regulation; D016678:Genome; D005938:Glucocorticoids / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D018836:Inflammation Mediators / Q000502:physiology; D011485:Protein Binding; D012333:RNA, Messenger / Q000032:analysis; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism*; D012307:Risk Factors; D012680:Sensitivity and Specificity; D015398:Signal Transduction / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation
D005938:Glucocorticoids; D018836:Inflammation Mediators; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D014157:Transcription Factors