Phosphoinositide 3-kinase/Akt and nuclear factor-kappaB are involved in Staphylococcus aureus-induced apoptosis in U937 cells.
OBJECTIVE
To explore the mechanisms involved in Staphylococcus aureus (S. aureus) invading human monocytic U937 cells.


METHODS
S. aureus were added to U937 cells at multiplicity of infections (MOI) of 20:1 for 0, 15, 30, 60, and 90 minutes, respectively. Cell apoptosis was analyzed with Hoechst 33258 staining and Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) flow cytometry analysis. Akt and nuclear factor-kappaB (NF-kappaB) activities were detected by Western blotting.


RESULTS
Infection of U937 cells with S. aureus induced rapid cell death in a time-dependent manner, and the cells displayed characteristic features of apoptosis. S. aureus-induced apoptosis was associated with a prominent downregulation of activated (phosphorylated) Akt and NF-kappaB. The inhibition of phosphorylated Akt by LY294002 led to the inhibition of NF-kappaB in a dose-dependent manner. Inhibition of Akt with LY294002 caused further increase in apoptosis of U937 cells.


CONCLUSIONS
S. aureus can stimulate the apoptosis of U937 cells. S. aureus induces apoptosis of U937 cells by inhibiting Akt-regulated NF-kappaB.
Wang
Jia-he
JH
Department of Geriatrics, Shengjing Hospital, China Medical University, Shenyang 110004, China. cmuwjh@126.com
Zhou
Yi-jun
YJ
Tian
Li
L
He
Ping
P
D017209:Apoptosis; D002867:Chromones / Q000494:pharmacology; D006801:Humans; D009025:Morpholines / Q000494:pharmacology; D016328:NF-kappa B / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000502:physiology*; D013211:Staphylococcus aureus / Q000472:pathogenicity*; D020298:U937 Cells
D002867:Chromones; D009025:Morpholines; D016328:NF-kappa B; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt