Mer regulates microglial/macrophage M1/M2 polarization and alleviates neuroinflammation following traumatic brain injury

被引：258

作者：

Wu, Haijian ^{[1
,2
,3
,4
]}

Zheng, Jingwei ^{[1
]}

Xu, Shenbin ^{[1
]}

Fang, Yuanjian ^{[1
]}

Wu, Yingxi ^{[3
,4
]}

Zeng, Jianxiong ^{[3
,4
]}

Shao, Anwen ^{[1
]}

Shi, Ligen ^{[1
]}

Lu, Jianan ^{[1
]}

Mei, Shuhao ^{[1
]}

Wang, Xiaoyu ^{[1
]}

Guo, Xinying ^{[3
,4
]}

Wang, Yirong ^{[2
]}

Zhao, Zhen ^{[3
,4
]}

Zhang, Jianmin ^{[1
,5
,6
]}

机构：

[1] Zhejiang Univ, Sch Med, Affiliated Hosp 2, Dept Neurosurg, 88 Jiefang Rd, Hangzhou 310009, Zhejiang, Peoples R China

[2] Zhejiang Univ, Sch Med, Sir Run Run Shaw Hosp, Dept Neurosurg, Hangzhou, Zhejiang, Peoples R China

[3] Univ Southern Calif, Keck Sch Med, Ctr Neurodegenerat & Regenerat, Zilkha Neurogenet Inst, 1501 San Pablo St, Los Angeles, CA 90089 USA

[4] Univ Southern Calif, Keck Sch Med, Dept Physiol & Biophys, 1501 San Pablo St, Los Angeles, CA 90089 USA

[5] Zhejiang Univ, Brain Res Inst, Hangzhou, Peoples R China

[6] Zhejiang Univ, Collaborat Innovat Ctr Brain Sci, Hangzhou, Peoples R China

来源：

JOURNAL OF NEUROINFLAMMATION | 2021年 / 18卷 / 01期

基金：

中国国家自然科学基金;

关键词：

Mer; Microglia; macrophage; M1; M2; polarization; Neuroinflammation; TBI; RECEPTOR TYROSINE KINASE; WHITE-MATTER; MICROGLIA/MACROPHAGE POLARIZATION; SEX-DIFFERENCES; MYELOID CELLS; TAM RECEPTOR; INFLAMMATION; MOUSE; MACROPHAGES; RESOLUTION;

D O I：

10.1186/s12974-020-02041-7

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Background Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Microglial/macrophage activation and neuroinflammation are key cellular events following TBI, but the regulatory and functional mechanisms are still not well understood. Myeloid-epithelial-reproductive tyrosine kinase (Mer), a member of the Tyro-Axl-Mer (TAM) family of receptor tyrosine kinases, regulates multiple features of microglial/macrophage physiology. However, its function in regulating the innate immune response and microglial/macrophage M1/M2 polarization in TBI has not been addressed. The present study aimed to evaluate the role of Mer in regulating microglial/macrophage M1/M2 polarization and neuroinflammation following TBI. Methods The controlled cortical impact (CCI) mouse model was employed. Mer siRNA was intracerebroventricularly administered, and recombinant protein S (PS) was intravenously applied for intervention. The neurobehavioral assessments, RT-PCR, Western blot, magnetic-activated cell sorting, immunohistochemistry and confocal microscopy analysis, Nissl and Fluoro-Jade B staining, brain water content measurement, and contusion volume assessment were performed. Results Mer is upregulated and regulates microglial/macrophage M1/M2 polarization and neuroinflammation in the acute stage of TBI. Mechanistically, Mer activates the signal transducer and activator of transcription 1 (STAT1)/suppressor of cytokine signaling 1/3 (SOCS1/3) pathway. Inhibition of Mer markedly decreases microglial/macrophage M2-like polarization while increases M1-like polarization, which exacerbates the secondary brain damage and sensorimotor deficits after TBI. Recombinant PS exerts beneficial effects in TBI mice through Mer activation. Conclusions Mer is an important regulator of microglial/macrophage M1/M2 polarization and neuroinflammation, and may be considered as a potential target for therapeutic intervention in TBI.

引用

页数：20

共 88 条

[1] Post-Injury Neuroprotective Effects of the Thalidomide Analog 3,6-Dithiothalidomide on Traumatic Brain Injury [J].