The soluble glucocorticoid-induced tumor necrosis factor receptor causes cell cycle arrest and apoptosis in murine macrophages

Biochem Biophys Res Commun. 2004 Mar 26;316(1):24-32. doi: 10.1016/j.bbrc.2004.02.012.

Abstract

In order to clarify the mechanism by which soluble GITR (sGITR) inhibits the survival of murine macrophages we examined its effect on the macrophage cell cycle. Soluble GITR induced G1 phase arrest followed by apoptosis. It also reduced the expression of cyclins D2 and A, and of cdk4, resulting in reduced cdk2 and cdk4 activities. These findings suggest that sGITR arrests division of the macrophages in G1 by lowering the activities of cdk2 and cdk4, and that this leads to apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis*
  • Cell Cycle / drug effects
  • Cell Division / drug effects
  • Cell Line
  • Cells, Cultured
  • Cyclin-Dependent Kinases / metabolism
  • Cyclins / metabolism
  • G1 Phase
  • Glucocorticoid-Induced TNFR-Related Protein
  • Macrophages / cytology
  • Macrophages / drug effects
  • Macrophages / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Nitric Oxide / physiology
  • Protein Structure, Tertiary
  • Receptors, Nerve Growth Factor / chemistry
  • Receptors, Nerve Growth Factor / genetics
  • Receptors, Nerve Growth Factor / physiology*
  • Receptors, Tumor Necrosis Factor / chemistry
  • Receptors, Tumor Necrosis Factor / genetics
  • Receptors, Tumor Necrosis Factor / physiology*
  • Recombinant Proteins / pharmacology

Substances

  • Cyclins
  • Glucocorticoid-Induced TNFR-Related Protein
  • Receptors, Nerve Growth Factor
  • Receptors, Tumor Necrosis Factor
  • Recombinant Proteins
  • Tnfrsf18 protein, mouse
  • Nitric Oxide
  • Cyclin-Dependent Kinases