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Gamma interferon down-regulates glucocorticoid receptor expression and attenuates hormone action in a human

L N Song1

  • 1Department of Pathophysiology, Second Military Medical University, 800 Xiang Yin Road, 200433, Shanghai, P.R. China.

Endocrine
|December 15, 2010
PubMed

Insights

Gamma interferon (IFN) down-regulates glucocorticoid receptors (GR) in human osteosarcoma cells by reducing GR mRNA levels. This leads to decreased sensitivity to glucocorticoids, impacting cell proliferation and alkaline phosphatase activity.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Immunology

Background:

  • Glucocorticoids are potent regulators of cellular functions, including proliferation and differentiation.
  • Glucocorticoid receptor (GR) expression is crucial for mediating these effects.
  • Interferons (IFNs) are cytokines with diverse biological activities, including immunomodulatory and anti-proliferative effects.

Purpose of the Study:

  • To investigate the effect of gamma interferon (IFN) on glucocorticoid receptor (GR) expression and function in HOS-8603 cells.
  • To elucidate the molecular mechanisms underlying IFN-induced changes in GR.
  • To assess the functional consequences of altered GR expression on glucocorticoid-mediated cellular responses.

Main Methods:

  • HOS-8603 cells were treated with varying concentrations and durations of IFN.
  • Glucocorticoid receptor (GR) number and binding affinity were assessed.
  • Messenger RNA (mRNA) levels of GR were quantified using RNA blot hybridization.
  • Glucocorticoid-induced effects on cell proliferation and alkaline phosphatase (AKP) activity were measured.

Main Results:

  • IFN treatment led to a dose- and time-dependent down-regulation of GR number in HOS-8603 cells.
  • GR binding affinity for glucocorticoids remained unchanged.
  • IFN significantly decreased GR mRNA levels, indicating a transcriptional or post-transcriptional regulation.
  • The inhibitory effect of glucocorticoids on cell proliferation and the induction of AKP activity were attenuated in the presence of IFN.

Conclusions:

  • Gamma interferon (IFN) down-regulates glucocorticoid receptor (GR) expression in HOS-8603 cells, primarily at the mRNA level.
  • This reduction in GR expression leads to impaired glucocorticoid-mediated cellular functions, including proliferation and AKP induction.
  • IFN influences GR activity, suggesting a potential role in modulating cellular responses to glucocorticoids in osteosarcoma.

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