2. Academic Validation
  3. Proinflammatory S100A9 Stimulates TLR4/NF-κB Signaling Pathways Causing Enhanced Phagocytic Capacity of Microglial Cells

Proinflammatory S100A9 Stimulates TLR4/NF-κB Signaling Pathways Causing Enhanced Phagocytic Capacity of Microglial Cells

  • Immunol Lett. 2023 Mar 2;S0165-2478(23)00034-2. doi: 10.1016/j.imlet.2023.02.008.
Xiaoyin Zhang 1,  Dan Sun 2,  Xin Zhou 1,  Ce Zhang 2,  Qing Yin 1,  Li Chen 1,  Yong Tang 1,  Yonggang Liu 3,  Ludmilla A Morozova-Roche 4
Affiliations

Affiliations

  • 1 Laboratory of stem cell and Tissue Engineering, Chongqing Medical University, 400016, Chongqing, China.
  • 2 State Key Laboratory of Photon-Technology in Western China Energy, Institute of Photonics and Photon Technology, Northwest University, 710127, Xi'an, China.
  • 3 Laboratory of stem cell and Tissue Engineering, Chongqing Medical University, 400016, Chongqing, China. Electronic address: [email protected].
  • 4 Department of Medical Biochemistry and Biophysics, Umeå University, 90187, Umeå, Sweden.
PMID: 36870421 DOI: 10.1016/j.imlet.2023.02.008
Abstract

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 μm 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-κB 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.

Keywords

Alzheimer's disease; Microglia; Neuroinflammation; Phagocytosis; S100A9.

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