髓样细胞表达的触发受体1抑制LPS应激下巨噬细胞的自噬

doi:10.13418/j.issn.1001-165x.2018.06.009

中国临床解剖学杂志 ›› 2018, Vol. 36 ›› Issue (6): 642-647.doi: 10.13418/j.issn.1001-165x.2018.06.009

髓样细胞表达的触发受体1抑制LPS应激下巨噬细胞的自噬

朱爱萍¹，　梁道淼²，　粟青¹，　李莉芳²，　贾哲²，　贺丽萍¹，　任翔¹，　孙国瑛^{1, 3}

1. 湖南师范大学医学院基础医学系，长沙 410013；　2. 湖南师范大学树达学院临床医学系，长沙 410013；
3. 中南大学基础医学院，长沙 410078

收稿日期:2018-06-26 出版日期:2018-11-25 发布日期:2018-12-29
通讯作者: 孙国瑛，硕士生导师， E-mail：sunguoying1029@hunnu.edu.cn
作者简介:共同第一作者：朱爱萍（1980-），湖南永州人，在读硕士，主要研究方向：呼吸系统疾病损伤与修复，E-mail：1182403303@qq.com；梁道淼（1997-），湖南长沙人，2015级临床医学专业在读本科，E-mail：1392352818@qq.com
基金资助:
湖南省自然科学基金(2018JJ3368)；中南大学博士后基金（160320001）；2017年度湖南省大学生研究性学习和创新性实验计划（项目序号1003）

Triggering receptor expressed on myeloid cells-1 inhibits autophagy of macrophages under LPS stress

ZHU Ai-ping¹, LIANG Dao-miao², SU Qing¹, LI Li-fang², JIA Zhe², HE Li-ping¹, REN Xiang¹, SUN Guo-ying^{1, 3}

1. Department of Basic Medicine, College of Medine, Hunan Normal University, Changsha 410013, China; 2. Department of Clinical Medicine, College of Shu Da, Hunan Normal University, Changsha 410013, China; 3. School of Basic Medical, Central South University, Changsha 410078, China

Received:2018-06-26 Online:2018-11-25 Published:2018-12-29

摘要/Abstract

摘要：

目的　观察髓样细胞表达的触发受体1（TREM-1）对脂多糖（LPS）应激下巨噬细胞自噬相关基因表达的影响。方法　观察LPS应激下的巨噬细胞TREM-1蛋白的表达。分别选用TREM-1的激动剂（MAB1187）和TREM-1的拮抗剂（LR12）作用于巨噬细胞，利用qPCR检测巨噬细胞自噬相关基因ATG7、ATG5、ATG12及自噬标志蛋白微管相关蛋白1轻链3（LC3）mRNA的表达；采用Western Blot检测巨噬细胞TREM-1、LC3Ⅱ/Ⅰ、ATG7蛋白的表达；采用免疫荧光检测在LPS应激与TREM-1激活的情况下，巨噬细胞的自噬标志蛋白LC3表达。结果　LPS（400 ng/mL、1000 ng/mL）应激下巨噬细胞TREM-1蛋白表达明显增加；LPS（1000 ng/mL）作用巨噬细胞24 h，巨噬细胞TREM-1蛋白表达达到峰值。LPS应激的巨噬细胞自噬基因ATG7、ATG5、ATG12及自噬标志分子LC3 mRNA表达均降低；当给予TREM-1拮抗剂后，巨噬细胞的ATG7、ATG5、ATG12、LC3 mRNA表达均升高，而采用TREM-1激动剂后，自噬基因表达被抑制。Western Blot检测结果显示，TREM-1可抑制LPS应激下巨噬细胞LC3 Ⅱ/Ⅰ、ATG7蛋白的表达。免疫荧光检测表明TREM-1激动剂可使巨噬细胞胞内的LC3蛋白表达量减少。结论　巨噬细胞胞膜上TREM-1激活后，可使巨噬细胞自噬减弱，提示LPS应激下的巨噬细胞TREM-1可能通过抑制巨噬细胞的正常自噬从而发挥炎症放大作用。

关键词: , 髓样细胞表达的触发受体-1, 　巨噬细胞, 　脂多糖, 　自噬

Abstract:

Objective　To observe the effect of TREM-1 on the expression of autophagy related genes in macrophages. Methods　The expression of TREM-1 protein in macrophages exposed to lipopolysaccharide (LPS) was observed. TREM-1 agonists (MAB1187) and TREM-1 antagonists (LR12) were used to regulate the activities of macrophage. qPCR was used to detect macrophage autophagy related protein ATG7, ATG5, ATG12, and microtubule associated protein 1 light chain 3 (LC3) mRNA, respectively. Expression of TREM-1, LC3 II/I, and ATG7 protein were detected by Western Blot. The expression of autophagy marker protein LC3 in macrophages under LPS stress and TREM-1 activation was detected by immunofluorescence.　Results　The expression of TREM-1 protein in macrophages was significantly increased under the stress of LPS (400 ng/mL, 1000 ng/mL), and the TREM-1 protein expression in macrophages reached a peak when LPS (1000 ng/mL) acted as macrophage 24 h. ATG7, ATG5, ATG12 and LC3 mRNA expression of macrophage were reduced by LPS stress. When TREM-1 antagonists were given, the expression of ATG7, ATG5, ATG12 and LC3 mRNA increased, and the autophagic gene expression of macrophage was reversed after the use of TREM-1 activator. Western Blot assay showed that TREM-1 inhibited the expression of LC3 II/I and ATG7 proteins in macrophages under LPS stress. Immunofluorescence assay showed that TREM-1 could reduce the content of LC3 protein in macrophages. Conclusions　The macrophage autophagy is inhibited after the activation of TREM-1 on the membrane of macrophage, suggesting that the TREM-1 of macrophage under LPS stress may play an inflammatory magnification by inhibiting the normal autophagy of macrophages.

Key words: , TREM-1, 　Macrophage, 　LPS, 　Autophagy

朱爱萍,梁道淼,粟青,李莉芳,贾哲,贺丽萍,任翔,孙国瑛. 髓样细胞表达的触发受体1抑制LPS应激下巨噬细胞的自噬[J]. 中国临床解剖学杂志, 2018, 36(6): 642-647.

ZHU Ai-ping, LIANG Dao-miao, SU Qing, LI Li-fang, JIA Zhe, HE Li-ping, REN Xiang, SUN Guo-ying. Triggering receptor expressed on myeloid cells-1 inhibits autophagy of macrophages under LPS stress[J]. Chinese Journal Of Clinical Anatomy, 2018, 36(6): 642-647.

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髓样细胞表达的触发受体1抑制LPS应激下巨噬细胞的自噬

Triggering receptor expressed on myeloid cells-1 inhibits autophagy of macrophages under LPS stress

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