C-jun N-terminal kinase-mediated signaling is essential for Staphylococcus aureus-induced U937 apoptosis.
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.
Wang
Jia-he
JH
Department of Geriatrics, Shengjing Hospital, China Medical University, Shenyang 110004, China. cmuwjh@126.com
Yu
Bo
B
Niu
Hui-yan
HY
Li
Hui
H
Zhang
Yi
Y
Wang
Xin
X
He
Ping
P
D000873:Anthracenes / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3 / Q000378:metabolism; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D008264:Macrophages / Q000166:cytology / Q000378:metabolism / Q000382:microbiology; D048055:Mitogen-Activated Protein Kinase 8 / Q000037:antagonists & inhibitors / Q000378:metabolism; D048056:Mitogen-Activated Protein Kinase 9 / Q000037:antagonists & inhibitors / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology*; D013211:Staphylococcus aureus / Q000502:physiology*; D020298:U937 Cells; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D000873:Anthracenes; C494826:BAX protein, human; D047428:Protein Kinase Inhibitors; D051028:bcl-2-Associated X Protein; C432165:pyrazolanthrone; D048056:Mitogen-Activated Protein Kinase 9; D048031:JNK Mitogen-Activated Protein Kinases; D048055:Mitogen-Activated Protein Kinase 8; C505407:CASP3 protein, human; D053148:Caspase 3