Glucocorticoid receptor in human respiratory epithelial cells.

Abstract

Inhaled and intranasal glucocorticoids (GCs) are the most common and effective drugs for controlling symptoms and airway inflammation in respiratory diseases such as allergic rhinitis, chronic rhinosinusitis with/without nasal polyps, and asthma, and the respiratory epithelium is a primary target of GC anti-inflammatory actions. GC effects are mediated through the GC receptor (GR). In humans, one single GR gene gives rise to two main GR products, namely GRalpha and GRbeta, which are subject to translational and posttranslational modifications. GRalpha is expressed in virtually all human cells and tissues, including respiratory epithelial cells, and - at least in vitro - is downregulated by GC. GRalpha mediates the anti-inflammatory actions of GC by activating transcription of anti-inflammatory genes through binding of GRalpha to glucocorticoid response elements (GRE) located in the promoter region of target genes, repressing transcription of proinflammatory genes through direct interaction between GRalpha and proinflammatory transcription factors, such as AP-1 and NF-kappaB (transrepression), and also by destabilizing the mRNA of proinflammatory mediators. GRbeta acts as a dominant negative inhibitor of GRalpha-mediated transactivation and transrepression in certain in vitro studies with transfected cells. The GRbeta message is expressed at low levels in numerous tissues and its protein is mainly expressed in inflammatory cells, although it has also been detected in airway epithelial cells. Increased GRbeta expression has been reported in bronchial asthma and nasal polyposis, and after incubation of cells with certain proinflammatory stimuli. However, the role of GRbeta in modulating GC sensitivity in vivo has been highly debated and is as yet unclear.

• Authors: Laura Pujolsa, Joaquim Mullol, Cèsar Picado
• Journal: Neuroimmunomodulation (Neuroimmunomodulation) Vol. 16 Issue 5 Pg. 290-9 ( 2009) ISSN: 1423-0216 [Electronic] Switzerland
• PMID: 19571590 (Publication Type: Journal Article, Review)
• Copyright: Copyright 2009 S. Karger AG, Basel.

Chemical References

• Glucocorticoids
• Inflammation Mediators
• Receptors, Glucocorticoid
• glucocorticoid receptor alpha
• glucocorticoid receptor beta

Topics

• Glucocorticoids (metabolism, pharmacology)
• Humans
• Immune Tolerance (drug effects, genetics, immunology)
• Inflammation (drug therapy, genetics, immunology)
• Inflammation Mediators (metabolism)
• Receptors, Glucocorticoid (drug effects, genetics, metabolism)
• Respiratory Mucosa (cytology, drug effects, metabolism)
• Respiratory System (drug effects, metabolism, physiopathology)