HMGB1 augments cognitive impairment in sepsis-associated encephalopathy by binding to MD-2 and promoting NLRP3-induced neuroinflammation

doi:10.1111/psyg.12794

	HMGB1 augments cognitive impairment in sepsis-associated encephalopathy by binding to MD-2 and promoting NLRP3-induced neuroinflammation
	Xiong, Yanan 1; Yang, Jilin 1; Tong, Haiyang 2; Zhu, Chenting 1; Pang, Yinhu 1
刊名	PSYCHOGERIATRICS
	2021-12-21
关键词	cognitive impairment HMGB1 MD-2 neuroinflammation NLRP3 sepsis-associated encephalopathy
ISSN号	1346-3500
DOI	10.1111/psyg.12794
通讯作者	Xiong, Yanan(xiongyanan0605@163.com)
英文摘要	Background Sepsis-associated encephalopathy (SAE) always manifests with severe inflammatory symptoms and cognitive impairment. High mobility group box 1 (HMGB1) is a pro-inflammatory cytokine. In this study we investigated the role of HMGB1 in SAE. Methods An SAE mouse model was established through cecal ligation and puncture surgery and then injected with adenovirus short hairpin RNA (Ad-sh)-HMGB1 or Ad-sh-myeloid differentiation protein (MD-2). The cognitive impairment and pathological injury in mice of different groups were evaluated using the Morris water maze experiment, Y-maze test, tail suspension test, fear conditioning test, and haematoxylin-eosin staining. The expressions of HMGB1 (fully reduced and disulfide (ds)HMGB1), MD-2, and NLRP3 in SAE mice were determined. Then, levels of inflammatory cytokines were measured. The binding relation between HMGB1 and MD-2 was predicted and certified. Additionally, MD-2 was downregulated to verify the role of the binding of HMGB1 and MD-2 in neuroinflammation and cognitive impairment in SAE. Results Expressions of HMGB1, MD-2, NLRP3, and inflammatory cytokines were enhanced in the SAE mouse model, which were in parallel with impaired cognitive function. HMGB1 silencing resulted in downregulated NLRP3 expression and alleviated neuroinflammation and cognitive impairment in SAE mice. Mechanically, dsHMGB1 bound to MD-2 to activate NLRP3, thereby exacerbating neuroinflammation and cognitive impairment in SAE mice. The limited binding of HMGB1 and MD-2 downregulated NLRP3 expression to alleviate neuroinflammation and cognitive impairment in SAE mice. Conclusion HMGB1 was overexpressed in SAE, and dsHMGB1 bound to MD-2 to activate NLRP3 inflammasome, inducing neuroinflammation and cognitive impairment in SAE.
WOS关键词	TARGET
WOS研究方向	Geriatrics & Gerontology ; Psychiatry
语种	英语
出版者	WILEY
WOS记录号	WOS:000731907300001
内容类型	期刊论文
源URL	[http://ir.hfcas.ac.cn:8080/handle/334002/126928]
专题	中国科学院合肥物质科学研究院
通讯作者	Xiong, Yanan
作者单位	1.Tongji Univ, Sch Med, Shanghai Tongji Hosp, Dept Emergency, 389 Xincun Rd, Shanghai 200092, Peoples R China 2.Chinese Acad Sci, Hefei Inst Phys Sci, Hefei, Peoples R China
推荐引用方式 GB/T 7714	Xiong, Yanan,Yang, Jilin,Tong, Haiyang,et al. HMGB1 augments cognitive impairment in sepsis-associated encephalopathy by binding to MD-2 and promoting NLRP3-induced neuroinflammation[J]. PSYCHOGERIATRICS,2021.
APA	Xiong, Yanan,Yang, Jilin,Tong, Haiyang,Zhu, Chenting,&Pang, Yinhu.(2021).HMGB1 augments cognitive impairment in sepsis-associated encephalopathy by binding to MD-2 and promoting NLRP3-induced neuroinflammation.PSYCHOGERIATRICS.
MLA	Xiong, Yanan,et al."HMGB1 augments cognitive impairment in sepsis-associated encephalopathy by binding to MD-2 and promoting NLRP3-induced neuroinflammation".PSYCHOGERIATRICS (2021).