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-κB（NF-κB） 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-κB.The inhibition of phosphorylated Akt by LY294002 led to the inhibition of NF-κB 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-κB.