Modulation of Glucocorticoid Receptor Function and Expression in Adolescent Moderate Asthma

Abstract

Background: Previous studies on adult asthmatics have shown that the disease is associated with alterations in glucocorticoid receptor (GR) function. Objectives: The aim of the present study was to examine GR functional properties in adolescent asthma of different severity. Therefore, we determined GR hormone binding parameters, e. g. the equilibrium dissociation constant (K(d)) and the number of binding sites (B(max)), as well as the level of receptor expression in mononuclear cells isolated from the peripheral blood of patients with mild/moderate persistent asthma. Methods: The GR hormone binding activity was assessed by whole-cell binding assay, while receptor expression was evaluated by quantitative Western blotting. Results: In peripheral blood mononuclear cells (PBMCs) of patients suffering from moderate asthma, the GR displayed higher K(d) and B(max) values (78.0 +/- 19.5 nM and 11,715 +/- 1,952 sites/cell, respectively; n = 17) in comparison to healthy subjects (23.8 +/- 7.7 nM and 6,124 +/- 1,369 sites/cell; n = 12) and mild asthmatics (22.4 +/- 8.0 nM and 4,840 +/- 776 sites/cell; n = 11). However, the GR protein level in PBMCs was found to be similar in the three study groups. Conclusion: The results provide data on GR expression and its functional status in inflammatory cells of pediatric asthmatic patients. In moderate asthma, functional characteristics of GR are altered, though the significance of these findings remains to be clarified. Copyright (c) 2008 S. Karger AG, Basel