Résumé
The glucocorticoid receptor (GR) belongs to a superfamily of ligand-regulated nuclear steroid hormone receptors. The steps in the signal transduction pathway leading to the biological effects of glucocorticoids (GCs) include sequentially binding of the steroid to the GR ligand binding domain (LBD), receptor transformation
1–3
, nuclear translocation and either positive or negative gene transactivation
4
. Rifampicin (RIF) is a macrocyclic antibiotic used as an antituberculosis agent
5
. As the incidence of tuberculosis has been increasing, in part because of the AIDS epidemic, a growing number of patients are being exposed to the adverse effects of this antibiotic
6
. Indeed, this compound, as are the GCs (ref. 7), is often implicated in noxious drug interactions, because of its strong ability to induce drug-metabolizing enzymes
8,9
. Moreover, in humans, RIF, as are the GCs (ref. 10), has been described as a potential immunodepressor, associated notably with the reduction of mitogenic responsiveness of human peripheral blood lymphocytes
11,12
. Here, we report that RIF activates the human glucocorticoid receptor (hGR). Transient expression of wild-type, deleted or mutated GRs; sucrose density gradient sedimentation; and the BIAcore technique strongly suggest that RIF binds to the receptor with the physiological consequence that this antibiotic acts as an immunodepressor. Given the wide use of RIF in the treatment of coinfection of tuberculosis and HIV, this report is highly relevant to current medical practice.