RT Journal Article
SR Electronic
T1 Rifampicin Is Not an Activator of the Glucocorticoid Receptor in A549 Human Alveolar Cells
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 841
OP 846
VO 55
IS 5
A1 Dany Jaffuel
A1 Pascal Demoly
A1 Claire Gougat
A1 Gisèle Mautino
A1 Jean Bousquet
A1 Marc Mathieu
YR 1999
UL http://molpharm.aspetjournals.org/content/55/5/841.abstract
AB 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. The American Society for Pharmacology and Experimental Therapeutics