Glucocorticoid receptor-binding characteristics in severe asthma.
The cellular mechanisms associated with severe asthma are still poorly understood. This study investigated the association between glucocorticoid-receptor (GR) alterations and continuous oral glucocorticoid therapy requirement in severe asthma. GR-binding affinity (Kd) and receptor number (n) in peripheral blood monocytes (PBM) obtained from 10 normal subjects, 10 untreated, intermittent asthmatics and 10 severe asthmatics were assessed. Moreover, one ability of dexamethasone to inhibit regulated on activation, T-cells expressed and secreted (RANTES) release by these cells in vitro was investigated. GR-binding characteristics were studied in PBM using a 3H dexamethasone ligand-binding assay and Scatchard analysis. RANTES release was measured in the supernatant of PBM at 24 h using an enzyme-linked immunosorbent assay. No significant differences in Kd and n were found between the three groups of patients. Dexamethasone in vitro was able to inhibit RANTES release (mean+/-SEM), with the same concentration/response curve in intermittent, untreated asthmatics (0.47+/-0.22 versus 1.64+/-0.31 ng x mL(-1)) and severe asthmatics (1.49+/-0.64 versus 2.59+/-0.77 ng x mL(-1)). This study showed that, despite long-term treatment with oral glucocorticoids, there was no evidence of abnormalities in glucocorticoid receptor-binding characteristics in severe asthma, and moreover, it was demonstrated that glucocorticoid receptors were functional in vitro.
Bonnans
C
C
Clinic of Respiratory Illness, INSERM U454-IFR 3, Arnaud de Villeneuve Hospital, CHU-Montpellier, France.
Chanez
P
P
Meziane
H
H
Godard
P
P
Bousquet
J
J
Vachier
I
I
D000284:Administration, Oral; D000328:Adult; D001249:Asthma / Q000188:drug therapy* / Q000503:physiopathology; D018946:Chemokine CCL5 / Q000032:analysis; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009000:Monocytes / Q000187:drug effects* / Q000502:physiology*; D011485:Protein Binding / Q000187:drug effects* / Q000502:physiology*; D011965:Receptors, Glucocorticoid / Q000187:drug effects* / Q000502:physiology*; D012720:Severity of Illness Index; D013997:Time Factors
D018946:Chemokine CCL5; D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D003907:Dexamethasone