Abstract
It has recently been reported that rifampicin activates the glucocorticoid receptor and acts as an immunosuppressive drug. Because rifampicin constitutes an essential part of pulmonary tuberculosis therapy, we have examined whether it triggers glucocorticoid-like effects in alveolar cells. We have used reporter gene assays to measure the trans-activating and trans-repressing capacity of the glucocorticoid receptor after treating A549 human alveolar cells with rifampicin. The data show that rifampicin neither activated transcription from a promoter containing a glucocorticoid response element nor repressed the activity of activator protein 1 and nuclear factor κB, which are transcription factors involved in the immune response. In addition, rifampicin was also unable to inhibit the expression of an endogenous gene that contains activator protein 1 and nuclear factor κB response elements and encodes the proinflammatory cytokine RANTES (regulated upon activation normal T expressed and secreted protein). Finally, nuclear translocation of the glucocorticoid receptor, which occurs after ligand binding, was not triggered by rifampicin. In contrast, the glucocorticoid dexamethasone scored positive in all corresponding control experiments. In conclusion, rifampicin is not an activator of the glucocorticoid receptor in A549 alveolar cells. Our results support the clinical observation that rifampicin is not an immunosuppressive drug and suggest that the current medical practice concerning this antibiotic should not be changed.
Footnotes
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Send reprint requests to: Dr. Pascal Demoly, Service des Maladies Respiratoires-INSERM U454, Hôpital Arnaud de Villeneuve, CHU de Montpellier, 34295 Montpellier Cedex 5, France. E-mail:demoly{at}montp.inserm.fr
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G.M. is supported by a grant from the Conseil Régional du Languedoc-Roussillon and by a grant from the Ministère de la Recherche.
- Abbreviations:
- RIF
- rifampicin
- GC
- glucocorticoid
- GRE
- glucocorticoid response element
- GR
- glucocorticoid receptor
- DEX
- dexamethasone
- AP-1
- activator protein 1
- NF-κB
- nuclear factor-κB
- RANTES
- regulated upon activation normal T expressed and secreted protein
- DTT
- dithiothreitol
- TNF-α
- tumor necrosis factor α
- TRE
- 12-O-tetradecanoyl-phorbol-13-acetate response element
- NF-κBRE
- NF-κB response element
- Received November 30, 1998.
- Accepted January 25, 1999.
- The American Society for Pharmacology and Experimental Therapeutics
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