2,6-dimethoxy-1,4-benzoquinone alleviates septic shock in mice by inhibiting NLRP3 inflammasome activation
10.12122/j.issn.1673-4254.2024.06.02
- VernacularTitle:2,6-二甲氧基-1,4-苯醌通过抑制NLRP3炎症小体活化缓解小鼠的感染性休克
- Author:
Wei ZHANG
1
,
2
;
Mengmeng DENG
;
Yao ZENG
;
Chenfei LIU
;
Feifei SHANG
;
Wenhao XU
;
Haoyi JIANG
;
Fengchao WANG
;
Yanqing YANG
Author Information
1. 蚌埠医科大学第一附属医院检验科,安徽 蚌埠 233004
2. 蚌埠医科大学慢性疾病免疫学基础与临床安徽省重点实验室,安徽 蚌埠 233030
- Keywords:
2,6-dimethoxy-1,4-benzoquinone;
NLRP3 inflammasome;
septic shock;
fermented wheat germ extract
- From:
Journal of Southern Medical University
2024;44(6):1024-1032
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the mechanism of 2,6-dimethoxy-1,4-benzoquinone(DMQ),an active ingredients in fermented wheat germ extract,for inhibiting NLRP3 inflammasome activation and alleviating septic shock in mice.Methods Cultured murine bone marrow-derived macrophages(BMDM)stimulated with lipopolysaccharide(LPS)were treated with DMQ,followed by treatment with Nigericin,ATP,and MSU for activating the canonical NLRP3 inflammasome;the non-canonical NLRP3 inflammasome was activated by intracellular transfection of LPS,and AIM2 inflammasome was activated using Poly A:T.In human monocytic THP-1 cells,the effect of Nigericin on inflammasome activation products was examined using Western blotting and ELISA.Co-immunoprecipitation was performed to explore the mechanism of DMQ-induced blocking of NLRP3 inflammasome activation.In a male C57BL/6J mouse model of LPS-induced septic shock treated with 20 and 40 mg/kg DMQ,the levels of IL-1β and TNF-α in the serum and peritoneal lavage fluid were determined using ELISA,and the survival time of the mice within 36 h was observed.Results Treatment with DMQ effectively inhibited LPS-induced activation of canonical NLRP3 inflammasome in mouse BMDM and human THP-1 cells and also inhibited non-canonical NLRP3 inflammasome activation in mouse BMDM,but produced no significant effect on AIM2 inflammasome activation.DMQ significantly blocked the binding between ASC and NLRP3.In the mouse models of septic shock,DMQ treatment significantly reduced the levels of IL-1β in the serum and peritoneal fluid and obviously prolonged survival time of the mice.Conclusion DMQ can effectively block ASC-NLRP3 interaction to inhibit NLRP3 inflammasome activation and alleviate LPS-induced septic shock in mice.
