Proinflammatory S100A9 stimulates TLR4/NF-?B signaling pathways causing enhanced phagocytic capacity of microglial cells

作者全名："Zhang, Xiaoyin; Sun, Dan; Zhou, Xin; Zhang, Ce; Yin, Qing; Chen, Li; Tang, Yong; Liu, Yonggang; Morozova-Roche, Ludmilla A."

作者地址："[Zhang, Xiaoyin; Zhou, Xin; Yin, Qing; Chen, Li; Tang, Yong; Liu, Yonggang] Chongqing Med Univ, Lab Stem Cell & Tissue Engn, Chongqing 400016, Peoples R China; [Sun, Dan; Zhang, Ce] Northwest Univ, Inst Photon & Photon Technol, State Key Lab Photon Technol Western China Energy, Xian 710127, Peoples R China; [Morozova-Roche, Ludmilla A.] Umea Univ, Dept Med Biochem & Biophys, S-90187 Umea, Sweden"

通信作者："Liu, YG (通讯作者)，Chongqing Med Univ, Lab Stem Cell & Tissue Engn, Chongqing 400016, Peoples R China."

来源：IMMUNOLOGY LETTERS

ESI学科分类：IMMUNOLOGY

WOS号：WOS:000951654500001

JCR分区：Q3

影响因子：3.3

年份：2023

卷号：255

期号：　

开始页：54

结束页：61

文献类型：Article

关键词：Microglia; Phagocytosis; Neuroinflammation; Alzheimer ?s disease

摘要："Alzheimer's disease (AD) is the main cause of dementia, affecting the increasingly aging population. Growing evidence indicates that neuro-inflammation plays crucial roles, e.g., the association between AD risk genes with innate immune functions. In this study, we demonstrate that moderate concentrations of pro-inflammatory cytokine S100A9 regulate immune response of BV2 microglial cells, i.e., the phagocytic capacity, reflected by elevated number of 1 mu m diameter Dsred-stained latex beads in the cytoplasm. In contrast, at high S100A9 concentrations, both the viability and phagocytic capacity of BV2 cells drop substantially. Furthermore, it is uncovered that S100A9 affects phagocytosis of microglia via NF-kappa B signaling pathways. Application of related target-specific drugs, i.e., IKK and TLR4 inhibitors, effectively suppresses BV2 cells' immune responses. These results suggest that pro-inflammatory S100A9 activates microglial phagocytosis, and possibly contributes to the clearance of amyloidogenic species at the early stage of AD."

基金机构："Natural Science Foundation of ShaanxiProvince [2021JM-301]; Youth Innovation Team of Future Medical Support Plan of Chongqing Medical University [W0037]; China Scholarship Council [202106970013]; Swedish Medical Research Council [2022-000638]; Infrastructure grant of Medical Faculty, Ume?; University (Ludmilla A Morozova-Roche)"

基金资助正文："Funding statement This work was supported by Natural Science Foundation of ShaanxiProvince (2021JM-301) , The Youth Innovation Team of Future Medical Support Plan of Chongqing Medical University (No. W0037) , China Scholarship Council (202106970013) , Swedish Medical Research Council (2022-000638) and Infrastructure grant of Medical Faculty, Ume? University (Ludmilla A Morozova-Roche) ."