TLR2/NF-kB signaling in macrophage/microglia mediated COVID-pain induced by SARS-CoV-2 envelope protein

被引:0
|
作者
Cui, Huan [1 ]
Sun, Fengrun [1 ]
Yu, Ning [1 ]
Cao, Yan [1 ]
Wang, Xue [1 ,2 ]
Zhang, Di [1 ,2 ]
Chen, Zhen [1 ,2 ]
Wang, Naili [1 ,2 ]
Yuan, Bo [1 ]
Liu, Penghao [3 ]
Duan, Wanru [3 ]
Qiu, Wenying [1 ,2 ]
Yin, Xiangsha [1 ,2 ]
Ma, Chao [1 ,2 ,4 ]
机构
[1] Chinese Acad Med Sci, Peking Union Med Coll, Sch Basic Med, State Key Lab Common Mech Res Major Dis,Dept Human, 5 DongDanSanTiao, Beijing 100005, Peoples R China
[2] Natl Human Brain Bank Dev & Funct, Beijing, Peoples R China
[3] Capital Med Univ, China Int Neurosci Inst CHINA INI, Lab Spinal Cord Injury & Funct Reconstruct, Dept Neurosurg,Xuanwu Hosp, Beijing, Peoples R China
[4] Chinese Inst Brain Res, Beijing 102206, Peoples R China
基金
中国国家自然科学基金;
关键词
COUGH;
D O I
10.1016/j.isci.2024.111027
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Pain has become a major symptom of long COVID-19 without effective therapy. Apart from viral infection pathological process, SARS-CoV-2 membranal proteins (envelope [S2E], spike [S2S] and membrane [S2M]) also present pro-inflammatory feature independently. Here, we aim to uncover the neuroinflammatory mechanism of COVID-pain induced by SARS-CoV-2 membranal proteins. We detected the three proteins in both peripheral sensory ganglions and spinal dorsal horn of COVID-19 donors. After intradermal and intrathecal injection, only S2E triggered pain behaviors, accompanied with upregulated-phosphorylation nuclear factor kappa B (NF-KB), K B), which was significantly attenuated by minocycline in mice. We further identified Toll-like receptor 2 (TLR2) among TLRs as the target of S2E to evoke inflammatory responses leading to COVID-pain. This study identified the nociceptive effect of S2E through directly interacting with macrophage/microglia TLR2 and inducing the following NF-KB K B inflammatory storm. Clearing away S2E and inhibiting macrophage/microglia TLR2 served as perspective therapeutic strategies for COVID-19 pain.
引用
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页数:21
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