Glucocorticoids induced down-regulation of glucocorticoid receptor mRNA expression in asthma.
Although their precise mechanism of action remains to be elucidated, glucocorticoids represent the most effective therapy in the treatment of asthma. Interactions between the glucocorticoid receptor and the AP-1 complex have been shown to regulate the transcription of some genes, including glucocorticoid receptor itself. The aim of the present study was to compare the expression of mRNA for glucocorticoid receptor in human blood monocytes obtained from seven unstable untreated asthmatic patients who were subsequently treated with high doses of parenteral corticosteroid (methyl prednisolone 120 mg/day) for 10 days. mRNA expression was identified after RNA extraction using RNAzol and analysed after reverse transcriptase, by polymerase chain reaction using a semiquantitative competitive hybridization assay. All asthmatic patients showed an improvement in their FEV1 values after corticosteroid treatment (per cent of predicted value 68.28 +/- 4.93 versus 95.57 +/- 6.41, P < 0.02), and a significant decrease for glucocorticoid receptor mRNA expression (P < 0.02) was observed in their monocytes. This is the first report of an ex vivo down-regulation for the glucocorticoid receptor mRNA expression, following corticosteroid treatment.
Vachier
I
I
Clinique des Maladies Respiratoires, CJF INSERM 9210, Hôpital Arnaud de Villeneuve, Montpellier, France.
Roux
S
S
Chanez
P
P
Loubatière
J
J
Térouanne
B
B
Nicolas
J C
JC
Godard
P
P
D000328:Adult; D000368:Aged; D001249:Asthma / Q000097:blood* / Q000188:drug therapy; D001483:Base Sequence; D015536:Down-Regulation; D005260:Female; D006801:Humans; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage* / Q000627:therapeutic use; D008875:Middle Aged; D008969:Molecular Sequence Data; D009000:Monocytes / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis*; D011965:Receptors, Glucocorticoid / Q000378:metabolism*
D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D008775:Methylprednisolone