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 alpha (GRalpha), which represses numerous genes encoding pro-inflammatory mediators. A hormone binding deficient GR isoform named GRbeta has been isolated in humans. When overexpressed by transfection, GRbeta may function as a dominant negative modulator of GRalpha. However, to act as such, GRbeta has to be more abundant than GRalpha, and conflicting data have been obtained concerning the relative levels of the two isoforms in cell lines and freshly isolated cells. Moreover, the dominant negative effect was not confirmed by independent laboratories. In GC-resistant asthmatics, GRbeta was expressed by an increased number of peripheral blood mononuclear cells (PBMCs), airway T cells, and cells found in skin biopsies of tuberculin responses. However, the relative amounts of GRalpha and GRbeta in these cells were not determined. In GC-dependent asthmatics, PBMCs expressed GRalpha predominantly. No cells containing higher levels of GRbeta than GRalpha have yet been reported in asthmatics. Even if the existence of such cells is demonstrated, the role of GRbeta in asthma will remain a matter of controversy because functional studies have given discrepant data.
Gagliardo
R
R
Istituto di Fisiopatologia Respiratoria, Consiglio Nazionale della Ricerche, Palermo, Italy.
Vignola
A M
AM
Mathieu
M
M
D001249:Asthma / Q000503:physiopathology*; D006801:Humans; D011965:Receptors, Glucocorticoid / Q000378:metabolism / Q000502:physiology*
D011965:Receptors, Glucocorticoid; C411470:glucocorticoid receptor alpha; C121943:glucocorticoid receptor beta