生物技术进展 ›› 2018, Vol. 8 ›› Issue (2): 169-173.DOI: 10.19586/j.2095-2341.2017.0140

• 研究论文 • 上一篇    下一篇

模式识别受体激活状态对小胶质细胞p38-MAPK磷酸化水平的影响

郑翰轩,张郃*   

  1. 首都医科大学宣武医院药剂科, 北京 100053
  • 收稿日期:2017-08-01 出版日期:2018-03-25 发布日期:2017-12-14
  • 通讯作者: 张郃,药师,硕士,主要研究方向为分子药理。E-mail:zhanghe0718@sina.com
  • 作者简介:郑翰轩,药师,主要研究方向为药学。E-mail: zhenghanxuan90@126.com。
  • 基金资助:
    北京市政府项目经费(20170026)资助。

Effect of Pattern Recognition Receptor Activation State on the p38-MAPK Phosphorylation in Microglia

ZHENG Hanxuan, ZHANG He   

  1. Department of Pharmacy, Xuanwu Hospital of Capital Medical University, Beijing 100053, China
  • Received:2017-08-01 Online:2018-03-25 Published:2017-12-14

摘要: 为了探讨小胶质细胞模式识别受体(pattern recognition receptor,PRR)激活状态对Aβ42诱导下的细胞应激性p38丝裂原活化蛋白激酶(p38-mitogen activated protein kinase,p38-MAPK)磷酸化及细胞吞噬能力的影响,在不同模式识别受体(SRA,TRL2,SRB,CD36)的抗体存在的条件下用寡聚物Aβ42蛋白(oAβ42)孵育并活化小胶质细胞,测定细胞活化后的p38-MAPK激酶磷酸化水平和小胶质细胞模式识别受体TLR2的阻断对细胞Aβ42吞噬量的影响。结果发现,与正常小胶质细胞对比,模式识别受体SRA(scavenger receptor A)及TLR2受体(toll-like receptor 2)被相应抗体阻断的小胶质细胞在受到Aβ42蛋白激活时,p38-MAPK的磷酸化水平显著降低;TLR2受体被其抗体阻断后小胶质细胞对Aβ42的吞噬量降低,说明该模式识别受体激活状态影响胶质细胞吞噬能力,该过程与p38-MAPK的磷酸化水平相关。而受体内吞抑制剂对小胶质细胞的Aβ42蛋白的吞入量没有显著影响,说明上述细胞对寡聚物Aβ42的吞入过程并非经典的受体内吞过程。TLR家族受体有望成为阿尔茨海默病(Alzheimei Disease, AD)免疫治疗的潜在治疗靶标。

关键词: 小胶质细胞, 模式识别受体, 磷酸化, 吞噬

Abstract: To investigate the effect of pattern recognition receptor(PRR) activation state on Aβ42-induced p38-MAPK phosphorylation and phagocytosis ability in microglia, normal microglia and PRR(SRA,TRL2,SRB,CD36)-blocked microglia was incubated with oligomer form of Aβ42(oAβ42). The level of p38-MAPK phosphorylation and the effect of the blocking of PRR in microglia on cell uptake of Aβ42 was measured. Results showed that, antibody-blocking SRA and TLR2 receptor reduced the p38-MAPK phosphorylation level induced by Aβ42 significantly, compared with normal microglia. Antibody-blocking toll-like receptor 2(TRL2) neutralization lower the cell uptake of Aβ42, which indicated that the PRR activation state had influenced the phagocytosis ability of microglia, and the process was related with the p38-MAPK phosphorylation level. However,endocytosis inhibiter-treated microglia had no significant influence on oAβ42 uptake amount, which indicated that endocytosis on Aβ42 was not classical endocytosis. Toll-like receptor 2(TLR2)was involved in oAβ42 phagocytosis initiation and would be potential therapeutic target for AD immunotherapy.

Key words: microglia, pattern recognition receptor, phosphorylation, phagocytosis