Glucocorticoid receptors in human airways.
Inhaled and intranasal glucocorticoids are the most common and effective drugs for controlling symptoms and airway inflammation in respiratory diseases such as asthma, allergic rhinitis, and nasal polyposis. The last few years have seen a growing understanding of the mechanisms of glucocorticoid action and, in particular, the receptor that mediates glucocorticoid actions, the glucocorticoid receptor (GR). In this revision we present an update on the GR gene, the expression and regulation of its gene products, namely GRalpha and GRbeta, as well as their alterations in pathological states. GRalpha is responsible for the induction and repression of target genes, it is expressed in virtually all human cells and tissues, and its expression is known to be downregulated by glucocorticoids. GRbeta has been found to act as a dominant negative inhibitor of GRalpha-mediated transactivation in in vitro studies with transfected cells, but it does not appear to have a significant inhibitory effect on GRalpha-mediated transrepression. In addition, for most tissues the expression of GRbeta, at least at the mRNA level, is extremely low compared with that of GRalpha. Some pro-inflammatory cytokines appear to upregulate the expression of GRbeta, and increased GRbeta expression has been reported in diseases associated with glucocorticoid resistance or insensitivity, such as bronchial asthma, nasal polyposis, and ulcerative colitis. However, the possible role of GRbeta in modulating glucocorticoid sensitivity and/or resistance in vivo has been highly debated and it is not yet clear.
Pujols
L
L
Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain.
Mullol
J
J
Torrego
A
A
Picado
C
C
D001249:Asthma / Q000235:genetics* / Q000276:immunology; D001980:Bronchi / Q000276:immunology; D015870:Gene Expression; D005786:Gene Expression Regulation; D006801:Humans; D009298:Nasal Polyps / Q000235:genetics / Q000276:immunology; D011965:Receptors, Glucocorticoid / Q000235:genetics* / Q000276:immunology; D012220:Rhinitis / Q000235:genetics* / Q000276:immunology
D011965:Receptors, Glucocorticoid