1. Academic Validation
  2. Peroxiredoxin 2 activates microglia by interacting with Toll-like receptor 4 after subarachnoid hemorrhage

Peroxiredoxin 2 activates microglia by interacting with Toll-like receptor 4 after subarachnoid hemorrhage

  • J Neuroinflammation. 2018 Mar 19;15(1):87. doi: 10.1186/s12974-018-1118-4.
Yue Lu 1 Xiang-Sheng Zhang 1 Zi-Huan Zhang 2 Xiao-Ming Zhou 3 Yong-Yue Gao 1 Guang-Jie Liu 1 Han Wang 4 Ling-Yun Wu 1 Wei Li 5 Chun-Hua Hang 6
Affiliations

Affiliations

  • 1 Department of Neurosurgery, Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China.
  • 2 Department of Neurosurgery, Zhongdu Hospital, Bengbu, China.
  • 3 Department of Neurosurgery, Changzheng Hospital, Second Military Medical University, Shanghai, China.
  • 4 Department of Neurosurgery, Jinling Hospital, School of Medicine, South Medical University, Nanjing, China.
  • 5 Department of Neurosurgery, Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China. lwxzlw@126.com.
  • 6 Department of Neurosurgery, Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China. hang_neurosurgery@163.com.
Abstract

Background: Peroxiredoxin (Prx) protein family have been reported as important damage-associated molecular patterns (DAMPs) in ischemic stroke. Since peroxiredoxin 2 (Prx2) is the third most abundant protein in erythrocytes and the second most protein in the cerebrospinal fluid in traumatic brain injury and subarachnoid hemorrhage (SAH) patients, we assessed the role of extracellular Prx2 in the context of SAH.

Methods: We introduced a co-culture system of primary neurons and microglia. Prx2 was added to culture medium with oxyhemoglobin (OxyHb) to mimic SAH in vitro. Neuronal cell viability was assessed by Lactate Dehydrogenase (LDH) assay, and neuronal Apoptosis was determined by TUNEL staining. Inflammatory factors in culture medium were measured by ELISA, and their mRNA levels in microglia were determined by qPCR. Toll-like Receptor 4 knockout (TLR4-KO) mice were used to provide TLR4-KO microglia; ST-2825 was used to inhibit MyD88, and pyrrolidine dithiocarbamate (PDTC) was used to inhibit NF-κB. Related cellular signals were analyzed by Western blot. Furthermore, we detected the level of Prx2 in aneurysmal SAH patients' cerebrospinal fluids (CSF) and compared its relationship with Hunt-Hess grades.

Results: Prx2 interacted with TLR4 on microglia after SAH and then activated microglia through TLR4/MyD88/NF-κB signaling pathway. Pro-inflammatory factors were expressed and released, eventually caused neuronal Apoptosis. The levels of Prx2 in SAH patients positively correlated with Hunt-Hess grades.

Conclusions: Extracellular Prx2 in CSF after SAH is a DAMP which resulted in microglial activation via TLR4/MyD88/NF-κB pathway and then neuronal Apoptosis. Prx2 in patients' CSF may be a potential indicator of brain injury and prognosis.

Keywords

Microglial activation; Neuronal apoptosis; Peroxiredoxin 2; Subarachnoid hemorrhage; Toll-like receptor 4.

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