Corticosterone suppresses the proliferation of RAW264.7 macrophage cells via glucocorticoid, but not mineralocorticoid, receptor

Biol Pharm Bull. 2013;36(4):592-601. doi: 10.1248/bpb.b12-00968. Epub 2013 Feb 6.

Abstract

Macrophages are white blood cells within tissues that are produced by monocytes and help to protect against infection by bacteria through phagocytosis. Several studies have shown a correlation between the state of depression and abnormalities in the immune response. Corticosterone (CORT), which is often referred to as the stress hormone, is a well-known regulator of peripheral immune responses and also shows anti-inflammatory properties in the body. However, it is still unclear how CORT regulates macrophage function. In this study, we focused on the effects of CORT on the proliferation and survival of macrophage cells using the macrophage cell line RAW264.7. Under treatment with 10 µM CORT for 24 h, the proliferation of RAW264.7 cells decreased to 73.6% of that in the control. Moreover, this inhibition was blocked by treatment with mifepristone, a glucocorticoid receptor (GR) antagonist, but not by spironolactone, a mineralocorticoid receptor (MR) antagonist. In an lactate dehydrogenase (LDH) assay, CORT did not show any cytotoxic effect on RAW264.7 cells. JC-1 cell staining also showed that CORT did not influence mitochondrial dysfunction in RAW264.7 cells. In an investigation of the modulation of a signaling cascade by CORT, treatment with CORT promoted the translocation of GR, but not MR, from the cytosol to the nucleus in RAW264.7 cells. In conclusion, our findings suggest that CORT suppresses the proliferation of RAW264.7 cells by controlling the transcription of a particular gene, which is related to cell proliferation, through the formation of a CORT-GR complex.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cell Proliferation / drug effects
  • Corticosterone / pharmacology*
  • Hormone Antagonists / pharmacology
  • Macrophages / cytology
  • Macrophages / drug effects*
  • Macrophages / metabolism
  • Membrane Potential, Mitochondrial / drug effects
  • Mice
  • Mifepristone / pharmacology
  • Mineralocorticoid Receptor Antagonists / pharmacology
  • Receptors, Glucocorticoid / antagonists & inhibitors
  • Receptors, Glucocorticoid / metabolism*
  • Receptors, Mineralocorticoid / metabolism
  • Spironolactone / pharmacology

Substances

  • Hormone Antagonists
  • Mineralocorticoid Receptor Antagonists
  • Receptors, Glucocorticoid
  • Receptors, Mineralocorticoid
  • Spironolactone
  • Mifepristone
  • Corticosterone