Glucocorticosteroids increase β2-adrenergic receptor transcription in human lung

Abstract

β2-Adrenergic receptors (β2R) are widely distributed and mediate a wide range of cellular responses in lung. Because glucocorticosteroids increase expression of β2R in cell lines, we have investigated the effects of glucocorticoids on the β2R mRNA level and the number of β2R in human peripheral lung in vitro. Incubation of lung tissues with dexamethasone (Dex) elevated both β2R mRNA level (as measured by Northern blot analysis) and β2R number (as measured by [125I]iodocyanopindolol binding). The increased accumulation of β2R mRNA could be detected at 15 min (1.27 ± 0.1-fold) and the maximal accumulation occurred at 2 h (2.73 ± 0.5-fold). The Dex-induced increase in β2R mRNA returned to the control level by 17 h. The increase in β2R number (1.58 ± 0.2-fold) was slower, reaching a maximum between 17 and 24 h. Dex increased β2R mRNA in a time- and concentration-dependent manner that was abolished by the steroid receptor antagonist mifepristone (RU-38486 or RU-486). The stability of β2R mRNA was unchanged by Dex, and a nuclear run-on assay revealed that Dex approximately doubled the transcriptional rate of the β2R gene. These observations suggest that glucocorticoids act on steroid receptors to increase β2R expression by increasing the rate of β2R gene transcription.