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 GR α and GR β , as well as their alterations in pathological states. GR α 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. GR β has been found to act as a dominant negative inhibitor of GR α ‐mediated transactivation in in vitro studies with transfected cells, but it does not appear to have a significant inhibitory effect on GR α ‐mediated transrepression. In addition, for most tissues the expression of GR β , at least at the mRNA level, is extremely low compared with that of GR α . Some pro‐inflammatory cytokines appear to upregulate the expression of GR β , and increased GR β 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 GR β in modulating glucocorticoid sensitivity and/or resistance in vivo has been highly debated and it is not yet clear.