ISSN:
1398-9995
Quelle:
Blackwell Publishing Journal Backfiles 1879-2005
Thema:
Medizin
Notizen:
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 GRα and GRβ, as well as their alterations in pathological states. GRα 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. GRβ has been found to act as a dominant negative inhibitor of GRα-mediated transactivation in in vitro studies with transfected cells, but it does not appear to have a significant inhibitory effect on GRα-mediated transrepression. In addition, for most tissues the expression of GRβ, at least at the mRNA level, is extremely low compared with that of GRα. Some pro-inflammatory cytokines appear to upregulate the expression of GRβ, and increased GRβ 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 GRβ in modulating glucocorticoid sensitivity and/or resistance in vivo has been highly debated and it is not yet clear.
Materialart:
Digitale Medien
URL:
http://dx.doi.org/10.1111/j.1398-9995.2004.00635.x
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