ZHZ-33-1 suppresses the macrophage inflammatory response triggered by Staphylococcus aureus infection
10.13431/j.cnki.immunol.j.20240122
- VernacularTitle:ZHZ-33-1抑制金黄色葡萄球菌感染引发巨噬细胞炎症反应的机制研究
- Author:
Yue ZHENG
1
;
Tingrong XIONG
;
Xiaoyan WU
;
Yu WANG
;
Xiaokai ZHANG
;
Hao ZENG
Author Information
1. 400038 重庆,陆军军医大学药学与检验医学系微生物与生化药学教研室国家免疫生物制品工程技术研究中心
- Publication Type:Journal Article
- Keywords:
Staphylococcus aureus;
ZHZ-33-1;
NF-κB;
MAPK
- From:
Immunological Journal
2024;40(12):877-882
- CountryChina
- Language:Chinese
-
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.
