DUSP1 regulates the induction of Staphylococcus aureus-mediated apoptosis in THP-1 macrophage cells

Abstract

Abstract Staphylococcus aureus (S. aureus) is a major human pathogen that causes apoptosis of immune cells during infections. The rate of apoptosis influences the severity and outcome of the disease, which can be fatal for infections including sepsis and septicemia. Dual specificity phosphatase-1 (DUSP1) is a negative regulator of MAPK signaling pathways in the host innate immune response, but its role in S. aureus-induced apoptosis remains unexplored. We used western blotting and immunofluorescence assays to show that S. aureus infection induced DUSP1 expression and promoted apoptosis in THP-1 cells. Knockdown of DUSP1 using an siRNA construct promoted the expression of key pro-apoptotic proteins, including cleaved-caspase3, cleaved-PARP1, cleaved-caspase9, cytochrome c and bax, whereas it inhibited the expression of key apoptosis inhibitory proteins bcl-2 and bcl-XL. These results were validated by flow cytometry. In addition, knockdown of DUSP1 promoted the accumulation of reactive oxygen species in S. aureus-induced macrophages, and mechanistically, knockdown of DUSP1 promoted the phosphorylation of target molecules in the MAPK signaling pathway, thereby promoting apoptosis in S. aureus-infected THP-1 macrophages. These data support a regulatory role for DUSP1 in S. aureus-mediated apoptosis and we suggest that DUSP1 be investigated as an anti-apoptotic therapeutic target.