Downregulation of SENP1 suppresses LPS-induced macrophage inflammation by elevating Sp3 SUMOylation and disturbing Sp3-NF-κB interaction.

Macrophages participate in all stages of sepsis and affect immune homeostasis and inflammatory processes. Small ubiquitin-like modifier (SUMO) protease SENP1 plays an important role in cellular inflammation by regulating proteins in SUMOylation. However, the roles and related mechanisms of SENP1 in macrophage inflammation during sepsis are largely unknown. In the present study, SENP1 expression was significantly promoted in lipopolysaccharide (LPS)-induced RAW 264.7 cells; furthermore, the knock down of SENP1 reduced the expression of inflammatory cytokines interleukin-6 and tumor necrosis factor-α. Momordin Ic (MC), a new type of SENP1 inhibitor, reduces LPS-induced cellular inflammation by depressing SENP1 expression. Moreover, the effect of SENP1 on LPS-induced inflammatory response was dependent on SENP1-Sp3 interaction and the promotion of Sp3 expression via Sp3 deSUMOylation. Furthermore, MC-depressed Sp3 expression disturbed Sp3-nuclear factor (NF)-κB interaction and then alleviated LPS-induced cellular inflammation. These results suggest that SENP1 promotes LPS-induced macrophage inflammation by promoting Sp3 expression via deSUMOylation and Sp3-NF-κB interaction in sepsis. AJTR