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  3. Microglial LOX-1/MAPKs/NF-κB positive loop promotes the vicious cycle of neuroinflammation and neural injury

Microglial LOX-1/MAPKs/NF-κB positive loop promotes the vicious cycle of neuroinflammation and neural injury

  • Int Immunopharmacol. 2019 May;70:187-200. doi: 10.1016/j.intimp.2019.02.013.
Xin Ge 1,  Dong-Mei Zhang 2,  Meng-Meng Li 1,  Yi Zhang 3,  Xiang-Yang Zhu 4,  Yong Zhou 4,  Xiao Peng 2,  Ai-Guo Shen 5
Affiliations

Affiliations

  • 1 Clinical Medicine Research Center, Affiliated Hospital 2 of Nantong University, Nantong 226001, People's Republic of China; Jiangsu Key Laboratory of Neurogeneration, Nantong University, Nantong 226001, People's Republic of China.
  • 2 Clinical Medicine Research Center, Affiliated Hospital 2 of Nantong University, Nantong 226001, People's Republic of China.
  • 3 Neurosurgery Department, Affiliated Hospital 2 of Nantong University, Nantong 226001, People's Republic of China.
  • 4 Neurology Department, Affiliated Hospital 2 of Nantong University, Nantong 226001, People's Republic of China.
  • 5 Clinical Medicine Research Center, Affiliated Hospital 2 of Nantong University, Nantong 226001, People's Republic of China; Jiangsu Key Laboratory of Neurogeneration, Nantong University, Nantong 226001, People's Republic of China; Cancer Research Center of Nantong, Tumor Hospital Affiliated to Nantong University, Nantong 226361, People's Republic of China. Electronic address: aiguoshen_nt@126.com.
PMID: 30807932 DOI: 10.1016/j.intimp.2019.02.013
Abstract

Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), a member of the scavenger receptor family, recognizes multiple ligands and participates in several inflammatory responses, but its function within the central nervous system (CNS) remains unclear. In this study, we discovered an increased LOX-1 expression in activated microglia in vivo and in vitro. Employing the specific inhibitors, we found that conditioned medium of necrotic neurons (Necrotic-CM) induced microglial LOX-1 expression through the MAPKs/NF-κB pathway. Silencing LOX-1 inhibited MAPK phosphorylation, NF-κB-p65 nuclear transportation, and pro-inflammatory factor production in microglia exposed to Necrotic-CM. Furthermore, utilizing the conditioned medium of activated microglia (MG-CM), we discovered microglial LOX-1 aggravated the neuroinflammation-induced neuronal Apoptosis. Collectively, a LOX-1/MPAKs/NF-κB positive loop might promote microglia activation and drive the vicious cycle of neuroinflammation and neuronal injury.

Keywords

LOX-1; MAPK; Microglia activation; NF-κB; Neural injury; Neuroinflammation.

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