C-jun N-terminal kinase-mediated signaling is essential for Staphylococcus aureus-induced U937 apoptosis

Chin Med Sci J. 2009 Mar;24(1):26-9. doi: 10.1016/s1001-9294(09)60054-7.

Abstract

Objective: To investigate the effect of SP600125, a specific c-jun N-terminal protein kinase (JNK) inhibitor, on Staphylococcus aureus (S. aureus)-induced U937 cell death and the underlying mechanism.

Methods: The human monocytic U937 cells were treated with S. aureus at different time with or without SP600125. Cell apoptosis was analyzed by flow cytometry. JNK, Bax, and caspase-3 activities were detected by Western blotting.

Results: S. aureus induced apoptosis in cultured U937 cells in a time-dependent manner. Expression of Bax and phospho-JNK significantly increased in S. aureus-treated U937 cells, and the level of activated caspase-3 also increased in a time-dependent manner. Inhibition of JNK with SP600125 significantly inhibited S. aureus-induced apoptosis in U937 cells.

Conclusions: S. aureus can induce apoptosis in U937 cells by phosphorylation of JNK and activation of Bax and caspase-3. SP600125 protects U937 cells from apoptosis induced by S. aureus via inhibiting the activity of JNK.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anthracenes / pharmacology
  • Apoptosis / physiology*
  • Caspase 3 / metabolism
  • Humans
  • JNK Mitogen-Activated Protein Kinases / metabolism*
  • Macrophages / cytology
  • Macrophages / metabolism
  • Macrophages / microbiology
  • Mitogen-Activated Protein Kinase 8 / antagonists & inhibitors
  • Mitogen-Activated Protein Kinase 8 / metabolism
  • Mitogen-Activated Protein Kinase 9 / antagonists & inhibitors
  • Mitogen-Activated Protein Kinase 9 / metabolism
  • Phosphorylation / drug effects
  • Protein Kinase Inhibitors / pharmacology
  • Signal Transduction / physiology*
  • Staphylococcus aureus / physiology*
  • U937 Cells
  • bcl-2-Associated X Protein / metabolism

Substances

  • Anthracenes
  • BAX protein, human
  • Protein Kinase Inhibitors
  • bcl-2-Associated X Protein
  • pyrazolanthrone
  • Mitogen-Activated Protein Kinase 9
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinase 8
  • CASP3 protein, human
  • Caspase 3