Phosphoinositide 3-kinase/Akt and nuclear factor-kappaB are involved in Staphylococcus aureus-induced apoptosis in U937 cells / 中国医学科学杂志(英文版)

ABSTRACT

<p><b>OBJECTIVE</b>To explore the mechanisms involved in Staphylococcus aureus (S. aureus) invading human monocytic U937 cells.</p><p><b>METHODS</b>S. aureus were added to U937 cells at multiplicity of infections (MOI) of 201 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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSIONS</b>S. aureus can stimulate the apoptosis of U937 cells. S. aureus induces apoptosis of U937 cells by inhibiting Akt-regulated NF-kappaB.</p>