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Reply to Rifampicin: a glucocorticoid receptor ligand?

Nature Medicine volume 4, pages 1090–1091 (1998)Cite this article

Calleja et al. reply—Genes encoding interleukin-2 and pro-opiomelanocortin (POMC) offer interesting models of negative regulation of gene transcription by glucocorticoids (GCs), but may differ considerably from other, more direct GC regulatory systems. In the POMC gene, binding of activated glucocorticoid receptors (GRs) to negative glucocorticoid response elements (nGREs) could lead to steric occlusion of positive transcription factors or activity3. In contrast, activated GR can directly interact with and inhibit transcription factors such as c-jun in activated Jurkat T-cells, leading to inhibition of interleukin-2 expression.

Ray et al. measured ACTH secretion, normally suppressed by GCs through the activated GR, and found that rifampicin had no effect. We agree that cell type is likely an important determinant of rifampicin activity. Indeed previous work has demonstrated a species specificity of rifampicin effects. Mouse and rat hepatocytes are refractory to rifampicin but not DEX-mediated induction of cytochrome P450 3A (CYP3A) genes4 or a GRE-driven reporter gene (unpublished data), in contrast to human hepatocytes5.

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References

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Authors and Affiliations

  1. INSERM U128 CNRS BP5051, 1919 Route de Mende, Montpellier, 34033, France

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

  2. UMR 9921 Faculté de Phamacie, 15 Avenue Flahault, Montpellier, 34060, France

    J.C. Mani

Authors
  1. C. Calleja
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  2. J.M. Pascussi
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  3. J.C. Mani
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  4. P. Maurel
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  5. M.J. Vilarem
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Calleja, C., Pascussi, J., Mani, J. et al. Reply to Rifampicin: a glucocorticoid receptor ligand?. Nat Med 4, 1090–1091 (1998). https://doi.org/10.1038/2762

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