Nimbolide targets RNF114 in treatment of mouse model of acute pneumonia caused by Staphylococcus aureus
10.16016/j.2097-0927.202312104
- VernacularTitle:印苦楝内酯靶向RNF114治疗金黄色葡萄球菌急性肺炎
- Author:
Hui SUN
1
;
Tian TIAN
;
Tingrong XIONG
;
Quanming ZOU
;
Xiaokai ZHANG
;
Xian YANG
;
Yu WANG
Author Information
1. 401331 重庆,重庆师范大学:生命科学学院活性物质生物技术教育部工程研究中心
- Keywords:
Staphylococcus aureus;
nimbolide;
macrophage;
RNF114
- From:
Journal of Army Medical University
2024;46(12):1353-1360
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the mechanism which drives nimbolide(NIM)in treating acute pneumonia caused by Staphylococcus aureus(S.auteus).Methods A mouse model of acute pneumonia caused by S.auteus was constructed through endotracheal intubation.After NIM treatment,the survival rate was observed,the amount of bacteria in the lung was tested by plate culture,and the expression of inflammatory cytokines in the lung tissues was detected with ELISA.After primary cultured peritoneal macrophages(PM)were infected with S.auteus,the effect of NIM on the expression of inflammatory cytokines and activation of inflammatory pathway were studied with ELISA and Western blotting,respectively.The effect of RNF114 knockdown by lentiviral shRNA infection on inflammation responses in PM was explored with ELISA and Western blotting.Results Acute infection of S.auteus in the lung could cause acute death in the mice,while NIM treatment significantly improved the survival rate and down-regulated the levels of inflammatory cytokines in the lung.However,it had no effect on the lung colonization of S.auteus in the short term.The results of in vitro experiments indicated that NIM may regulate RNF114 function to down-regulate the phosphorylation level of ERK,inhibit the activation of MAPK pathway,and thus suppress the expression of inflammatory cytokines.Conclusion NIM may inhibit the activation of MAPK pathway by regulating the function of RNF114,and thus suppress the expression of inflammatory cytokines in the lung,and finally inhibit the death of mice with acute pulmonary hyperinflammation caused by S.auteus.
