TREM1 Regulates Neuroinflammatory Injury by Modulate Proinflammatory Subtype Transition of Microglia and Formation of Neutrophil Extracellular Traps via Interaction With SYK in Experimental Subarachnoid Hemorrhage.
TREM1 Regulates Neuroinflammatory Injury by Modulate Proinflammatory Subtype Transition of Microglia and Formation of Neutrophil Extracellular Traps via Interaction With SYK in Experimental Subarachnoid Hemorrhage.
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在实验性蛛网膜下腔出血中，TREM1 通过与 SYK 相互作用调节小胶质细胞促炎亚型转变和中性粒细胞胞外陷阱的形成，从而调节神经炎症损伤
DOI：
10.3389/fimmu.2021.766178
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发表时间：
2021
影响因子：
7.3
通讯作者：
Chen G
中科院分区：
文献类型：
--
作者：
Wu X;Zeng H;Xu C;Chen H;Fan L;Zhou H;Yu Q;Fu X;Peng Y;Yan F;Yu X;Chen G
神经炎症是蛛网膜下腔出血（SAH）发病的关键过程，也是导致患者预后不良的原因之一。本研究旨在探讨触发受体表达于髓样细胞1 （TREM1）在SAH中的作用及其潜在机制。在我们的研究中，SAH后血浆可溶性TREM1水平显著升高，并与SAH严重程度和血清c反应蛋白相关。TREM1抑制肽LP17减轻了SAH后的神经功能缺损，降低了脑含水量，减轻了神经元损伤。同时，TREM1抑制肽通过减弱小胶质细胞的促炎亚型转化（CD68、CD16、CD86等标志物水平降低）和减少中性粒细胞胞外陷阱的形成（CitH3、MPO、NE等标志物水平降低），减轻神经炎症（IL-6、IL-1β、TNF-α等标志物水平降低）。进一步的机制研究发现TREM1可以通过与脾酪氨酸激酶（SYK）相互作用激活下游的促炎途径。综上所述，抑制TREM1通过与SYK相互作用，减轻小胶质细胞的促炎亚型转变，减少中性粒细胞胞外陷阱的形成，从而减轻神经炎症。TREM1可能是SAH的一个有希望的治疗靶点。
Neuroinflammation is a key process in the pathogenesis of subarachnoid hemorrhage (SAH) and contributes to poor outcome in patients. The purpose of this study is to explore the effect of triggering receptor expressed on myeloid cells 1 (TREM1) in the SAH, as well as its potential mechanism. In our study, plasma levels of soluble TREM1 was increased significantly after SAH and correlated to SAH severity and serum C-reactiveprotein. TREM1 inhibitory peptide LP17 alleviated the neurological deficits, attenuated brain water content, and reduced neuronal damage after SAH. Meanwhile, TREM1 inhibitory peptide decreased neuroinflammation (evidenced by the decreased levels of markers including IL-6, IL-1β, TNF-α) by attenuating proinflammatory subtype transition of microglia (evidenced by the decreased levels of markers including CD68, CD16, CD86) and decreasing the formation of neutrophil extracellular traps (evidenced by the decreased levels of markers including CitH3, MPO, and NE). Further mechanistic study identified that TREM1 can activate downstream proinflammatory pathways through interacting with spleen tyrosine kinase (SYK). In conclusion, inhibition of TREM1 alleviates neuroinflammation by attenuating proinflammatory subtype transition of microglia and decreasing the formation of neutrophil extracellular traps through interacting with SYK after SAH. TREM1 may be a a promising therapeutic target for SAH.
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影响因子：
11.4
作者：
Fan H;Ding R;Liu W;Zhang X;Li R;Wei B;Su S;Jin F;Wei C;He X;Li X;Duan C
通讯作者：
Duan C
影响因子：
8.3
作者：
He Y;Xu L;Li B;Guo ZN;Hu Q;Guo Z;Tang J;Chen Y;Zhang Y;Tang J;Zhang JH
通讯作者：
Zhang JH
影响因子：
8.3
作者：
Lu Q;Liu R;Sherchan P;Ren R;He W;Fang Y;Huang Y;Shi H;Tang L;Yang S;Zhang JH;Tang J
通讯作者：
Tang J
影响因子：
30.5
作者：
Liu, Qingkun;Johnson, Emily M.;Andreasson, Katrin I.
通讯作者：
Andreasson, Katrin I.
DOI：
10.1016/j.bbi.2016.02.007
发表时间：
2016-05
期刊：
Brain, behavior, and immunity
影响因子：
--
作者：
Provencio JJ;Swank V;Lu H;Brunet S;Baltan S;Khapre RV;Seerapu H;Kokiko-Cochran ON;Lamb BT;Ransohoff RM
通讯作者：
Ransohoff RM