Effect of Proinflammatory S100A9 Protein on Migration and Proliferation of Microglial Cells

作者全名："Bai, Qiao; Sun, Dan; Zeng, Yang; Zhu, Jie; Zhang, Ce; Zhang, Xiaoyin; Chen, Li; Zhou, Xin; Ye, Liu; Tang, Yong; Liu, Yonggang; Morozova-Roche, Ludmilla A."

作者地址："[Bai, Qiao; Zhang, Xiaoyin; Chen, Li; Zhou, Xin; Ye, Liu; Tang, Yong; Liu, Yonggang] Chongqing Med Univ, 1 Med Coll Rd, Chongqing, Peoples R China; [Sun, Dan; Zeng, Yang; Zhu, Jie; Zhang, Ce] Northwest Univ, Inst Photon & Photon Technol, State Key Lab Photon Technol Western China Energy, Xian, Shaanxi, Peoples R China; [Morozova-Roche, Ludmilla A.] Umea Univ, Dept Med Biochem & Biophys, Umea, Sweden"

通信作者："Liu, YG (通讯作者)，Chongqing Med Univ, 1 Med Coll Rd, Chongqing, Peoples R China."

来源：JOURNAL OF MOLECULAR NEUROSCIENCE

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:001101691400001

JCR分区：Q2

影响因子：2.8

年份：2023

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：Neuroinflammation; Alzheimer's disease; S100A9; Amyloid beta peptide; Interleukin

摘要："Alzheimer's disease (AD) is a multifactorial disease affecting aging population worldwide. Neuroinflammation became a focus of research as one of the major pathologic processes relating to the disease onset and progression. Proinflammatory S100A9 is the central culprit in the amyloid-neuroinflammatory cascade implicated in AD and other neurodegenerative diseases. We studied the effect of S100A9 on microglial BV-2 cell proliferation and migration. The responses of BV-2 cells to S100A9 stimulation were monitored in real-time using live cell microscopy, transcriptome sequencing, immunofluorescence staining, western blot analysis, and ELISA. We observed that a low dose of S100A9 promotes migration and proliferation of BV-2 cells. However, acute inflammatory condition (i.e., high S100A9 doses) causes diminished cell viability; it is uncovered that S100A9 activates TLR-4 and TLR-7 signaling pathways, leading to TNF-alpha and IL-6 expression, which affect BV-2 cell migration and proliferation in a concentration-dependent manner. Interestingly, the effects of S100A9 are not only inhibited by TNF-alpha and IL-6 antibodies. The addition of amyloid-beta (A beta) 1-40 peptide resumes the capacities of BV-2 cells to the level of low S100A9 concentrations. Based on these results, we conclude that in contrast to the beneficial effects of low S100A9 dose, high S100A9 concentration leads to impaired mobility and proliferation of immune cells, reflecting neurotoxicity at acute inflammatory conditions. However, the formation of A beta plaques may be a natural mechanism that rescues cells from the proinflammatory and cytotoxic effects of S100A9, especially considering that inflammation is one of the primary causes of AD."

基金机构："National Natural Science Foundation of China [51927804]; China Scholarship Council [202106970013]; Natural Science Foundation of Shaanxi Province [2021JM-301]; Youth Innovation Team of Future Medical Support Plan of Chongqing Medical University [W0037]; Swedish Medical Research Council and Infrastructure grant of Medical Faculty, Umea University"

基金资助正文："This work was supported by the National Natural Science Foundation of China (51927804), the China Scholarship Council (202106970013), the Natural Science Foundation of Shaanxi Province (2021JM-301), the Youth Innovation Team of Future Medical Support Plan of Chongqing Medical University (No. W0037), and the Swedish Medical Research Council and Infrastructure grant of Medical Faculty, Umea University (Ludmilla A Morozova-Roche)."