ZHZ-33-1 suppresses the macrophage inflammatory response triggered by Staphylococcus aureus infection

ZHENG Yue; XIONG Tingrong; WU Xiaoyan; WANG Yu; ZHANG Xiaokai; ZENG Hao

doi:10.13431/j.cnki.immunol.j.20240122

Abstract：Objective To investigate the regulatory effect and mechanism of new skeleton small molecule compound ZHZ-33-1 on the inflammatory response induced by primary macrophages in mice infected by Staphylococcus aureus.Methods qRT-PCR was used to detect the mRNA expression levels of inflammatory factors Tnf,Illb,116,Il12p40 in macrophages cells.The protein levels of TNF-α,IL-1 β,IL-6 and IL-12 in cell supernatant were determined by ELISA.Western blot was used to analyze the phosphorylation of key signaling pathway proteins such as NF-κB and MAPK.CCK8 detection was used to evaluate the effect of ZHZ-33-1 on macrophages activity.The OD600nm method was used to investigate the effect of ZHZ-33-1 on the growth of Staphylococcus aureus.Results 80 pmol/L ZHZ-33-1 had no significant effect on bacterial proliferation(P＞0.05)and cytotoxicity of macrophages(P＞0.05).Compared with the DMSO group,ZHZ-33-1 significantly inhibited the transcription and expression levels of inflammatory cytokines(TNF-α,IL-iβ,IL-6,and IL-12)in primary macrophages infected by Staphylococcus aureus(USA300)(P＜0.05).Further studies showed that ZHZ-33-1 was able to inhibit the NF-κB and MAPK pathways of wild macrophages,but was not TLR2-/-macrophages.Conclusion Through inhibiting NF-κB and MAPK signaling pathways,ZHZ-33-1 may inhibit the macrophages inflammatory response caused by Staphylococcus aureus.Therefore,ZHZ-33-1 is expected to become a new drug candidate for the treatment of Staphylococcus aureus-induced hyperinflammatory response.