TREM2 inhibits inflammatory responses in mouse microglia by suppressing the PI3K/NF-κB signaling.
TREM2 inhibits inflammatory responses in mouse microglia by suppressing the PI3K/NF-κB signaling.
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DOI：
10.1002/cbin.10975
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发表时间：
2019-04
影响因子：
3.9
通讯作者：
An X
中科院分区：
文献类型：
--
作者：
Li C;Zhao B;Lin C;Gong Z;An X
本研究旨在研究髓样细胞表达触发受体2（TREM2）对脂多糖（LPS）诱导BV2小胶质细胞产生促炎介质和细胞因子的影响。使用TREM2表达或TREM2特异性siRNA来诱导TREM2过表达或沉默。用PI3 K抑制剂LY294002预处理BV2细胞1小时，并用LPS刺激24小时。然后，分别测定细胞活力、凋亡、吞噬作用、一氧化氮（NO）、乳酸脱氢酶（LDH）和细胞因子产生，以及AKT和NF-κ B的活化。我们发现，LPS刺激显着降低BV2细胞的活力，增强BV2细胞吞噬和凋亡相比，对照组。此外，LPS刺激显著增加NO、LDH、TNF-α、IL-1 β的产生以及AKT和NF-κ B的活化，同时降低IL-10和TGF-β 1的水平。然而，这些促炎作用通过TREM2过表达或用LY294002预处理而显著减弱，而通过TREM2沉默而增强。因此，我们得出结论，TREM2通过下调BV2小胶质细胞中的PI3 K/AKT和NF-kB信号传导来抑制神经炎症。总之，治疗性增强TREM2表达可能是干预神经炎性疾病的新策略。
This study aimed to investigate the effects of triggering receptor expressed on myeloid cell‐2 (TREM2) on the production of pro‐inflammatory mediators and cytokines induced by lipopolysaccharide (LPS) in BV2 microglia. TREM2 expression or TREM2‐specific siRNA were used to induce TREM2 overexpression or silencing. The BV2 cells were pre‐treated with the PI3 K inhibitor of LY294002 for 1 h and stimulated with LPS for 24 h. Then, the cell viability, apoptosis, phagocytosis, nitric oxide (NO), lactate dehydrogenase (LDH), and cytokine production, as well as the activation of AKT and NF‐kB were determined, respectively. We found LPS stimulation significantly reduced BV2 cell viability, enhanced BV2 cell phagocytosis and apoptosis compared to the control groups. In addition, LPS stimulation significantly increased the production of NO, LDH, TNF‐α, IL‐1β, and the activation of AKT and NF‐kB, while decreased the levels of IL‐10 and TGF‐β1. However, these pro‐inflammatory effects were significantly attenuated by TREM2 overexpression or pre‐treatment with LY294002, while enhanced by TREM2 silencing. Thus, we concluded that TREM2 inhibited neuroinflammation by down‐regulating PI3 K/AKT and NF‐kB signaling in BV2 microglia. Above all, therapeutic enhanced TREM2 expression may be a new strategy for intervention of neuroinflammatory diseases.
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DOI：
10.1084/jem.20142322
发表时间：
2015-03-09
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Jay TR;Miller CM;Cheng PJ;Graham LC;Bemiller S;Broihier ML;Xu G;Margevicius D;Karlo JC;Sousa GL;Cotleur AC;Butovsky O;Bekris L;Staugaitis SM;Leverenz JB;Pimplikar SW;Landreth GE;Howell GR;Ransohoff RM;Lamb BT
通讯作者：
Lamb BT
影响因子：
7.3
作者：
Peng Q;Malhotra S;Torchia JA;Kerr WG;Coggeshall KM;Humphrey MB
通讯作者：
Humphrey MB
DOI：
10.1083/jcb.200808080
发表时间：
2009-01-26
期刊：
The Journal of cell biology
影响因子：
--
作者：
N'Diaye EN;Branda CS;Branda SS;Nevarez L;Colonna M;Lowell C;Hamerman JA;Seaman WE
通讯作者：
Seaman WE
影响因子：
5.4
作者：
Park, Hye Young;Kim, Gi-Young;Choi, Yung Hyun
通讯作者：
Choi, Yung Hyun
影响因子：
3.3
作者：
Tong, G.;Krauss, A.;Schmitt, K. R. L.
通讯作者：
Schmitt, K. R. L.