Microglia activation triggers oligodendrocyte precursor cells apoptosis via HSP60

Li,Yunhong; Zhang,Rui; Hou,Xiaolin; Zhang,Yumei; Ding,Feijia; Li,Fan; Yao,Yao; Wang,Yin

doi:10.3892/mmr.2017.6673

Microglia activation triggers oligodendrocyte precursor cells apoptosis via HSP60

Authors:
- Yunhong Li
- Rui Zhang
- Xiaolin Hou
- Yumei Zhang
- Feijia Ding
- Fan Li
- Yao Yao
- Yin Wang
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Affiliations: Ningxia Key Laboratory of Cerebrocranial Diseases, Basic Medical College of Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China, Department of Neurology, The General Hospital of Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China
Published online on: June 1, 2017 https://doi.org/10.3892/mmr.2017.6673
Pages: 603-608
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Reactive microglia are present in lesions of myelin‑associated white matter disorders resulting in injuries to oligodendrocyte precursor cells (OPCs). Therefore, protection of OPCs from injury due to excessive activation of microglia is important in treating these diseases. Heat shock protein 60 (HSP60) has been demonstrated to be released extracellularly in the failing heart upon stress or injury. However, the role of HSP60 in the central nervous system and whether it participates in the toxic effects of microglia on OPCs remains unclear. The present study used the co‑culture, cell death assays, binding assays, immunochemistry, western blot and ELISA. HSP60 was demonstrated to be released extracellularly by LPS‑activated microglia and to bind to OPCs, triggering OPC apoptosis. When pretreated with toll‑like receptor (TLR) 4 blocking antibody, the viability of OPCs increased, while the expression of nuclear factor κB (NFκB), caspase 3 and the release of proinflammatory cytokines triggered by HSP60 decreased. These results suggest that HSP60 released by microglia may mediate OPC apoptosis through binding to TLR4 on the surface of OPCs and subsequently activating the TLR4‑NFκB signaling pathway. HSP60 may, therefore, serve as a potential target for treatment of myelin‑associated neurodegenerative diseases that are accompanied by microglia activation.

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