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The antibiotic rifampicin is a nonsteroidal ligand and activator of the human glucocorticoid receptor

Nature Medicine volume 4, pages 92–96 (1998)Cite this article

Abstract

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 transformation1–3, nuclear translocation and either positive or negative gene transactivation4. Rifampicin (RIF) is a macrocyclic antibiotic used as an antituberculosis agent5. 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 antibiotic6. 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 enzymes8,9. 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 lymphocytes11,12. 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.

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Author notes

  1. C. Calleja and J.M. Pascussi: C.C and J.M.P contributed equally to this work.

Authors and Affiliations

  1. INSERM Unité 128, IFR 24, CNRS BP 5051, 1919 Route de Mende, 34293, Montpellier, France

    C. Calleja, J.M. Pascussi, P. Maurel & M.J. Vilarem

  2. UMR 9921, Faculté de Pharmacie, 15 avenue Flahault, 34060, Montpellier, cedex 1, France

    J.C. Mani

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  1. C. Calleja
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Correspondence to M.J. Vilarem.

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Calleja, C., Pascussi, J., Mani, J. et al. The antibiotic rifampicin is a nonsteroidal ligand and activator of the human glucocorticoid receptor. Nat Med 4, 92–96 (1998). https://doi.org/10.1038/nm0198-092

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