Is there a role for glucocorticoid receptor beta in asthma?

Glucocorticoids (GCs) are routinely used as anti-inflammatory drugs in the treatment of asthma. They act through binding to glucocorticoid receptor al pha (GR alpha), which represses numerous genes encoding pro-inflammatory me diators. A hormone binding deficient GR isoform named GR beta has been isol ated in humans. When overexpressed by transfection, GR beta may function as a dominant negative modulator of GR alpha. However, to act as such, GR bet a has to be more abundant than GR alpha, and conflicting data have been obt ained concerning the relative levels of the two isoforms in cell lines and freshly isolated cells. Moreover, the dominant negative effect was not conf irmed by independent laboratories. In GC-resistant asthmatics, GR beta was expressed by an increased number of peripheral blood mononuclear cells (PBM Cs), airway T cells, and cells found in skin biopsies of tuberculin respons es. However, the relative amounts of GR alpha and GR beta in these cells we re not determined. In GC-dependent asthmatics, PBMCs expressed GR alpha pre dominantly. No cells containing higher levels of GR beta than GR alpha have yet been reported in asthmatics. Even if the existence of such cells is de monstrated, the role of GR beta in asthma will remain a matter of controver sy because functional studies have given discrepant data.