GLUCOCORTICOIDS INDUCED DOWN-REGULATION OF GLUCOCORTICOID RECEPTOR MESSENGER-RNA EXPRESSION IN ASTHMA

Although their precise mechanism of action remains to be elucidated, g lucocorticoids represent the most effective therapy in the treatment o f 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 stud y was to compare the expression of mRNA for glucocorticoid receptor in human blood monocytes obtained from seven unstable untreated asthmati c patients who were subsequently treated with high doses of parenteral corticosteroid (methyl prednisolone 120 mg/day) for 10 days. mRNA exp ression was identified after RNA extraction using RNAzol and analysed after reverse transcriptase, by polymerase chain reaction using a semi quantitative competitive hybridization assay. All asthmatic patients s howed an improvement in their FEV(1) values after corticosteroid treat ment (per cent of predicted value 68.28 +/- 4.93 versus 95.57 +/- 6.41 , P < 0.02), and a significant decrease for glucocorticoid receptor mR NA expression (P < 0.02) was observed in their monocytes. This is the first report of an ex vivo down-regulation for the glucocorticoid rece ptor mRNA expression, following corticosteroid treatment.