HMGB1 mediates microglia activation via the TLR4/NF-κB pathway in coriaria lactone induced epilepsy

Shi,Yunbo; Zhang,Lingli; Teng,Junfang; Miao,Wang

doi:10.3892/mmr.2018.8485

HMGB1 mediates microglia activation via the TLR4/NF-κB pathway in coriaria lactone induced epilepsy

Authors:
- Yunbo Shi
- Lingli Zhang
- Junfang Teng
- Wang Miao
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Affiliations: Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China, Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China
Published online on: January 25, 2018 https://doi.org/10.3892/mmr.2018.8485
Pages: 5125-5131
Copyright: © Shi et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Epilepsy is a chronic and recurrent disease of the central nervous system, with a complex pathology. Recent studies have demonstrated that the activation of glial cells serve an important role in the development of epilepsy. The objective of the present study was to investigate the role of high‑mobility group box‑1 (HMGB1) in mediating the activation of glial cells through the toll‑like receptor 4 (TLR4)/nuclear factor (NF)‑κB signaling pathway in seizure, and the underlying mechanism. The brain tissue of post‑surgery patients with intractable epilepsy after resection and the normal control brain tissue of patients with craniocerebral trauma induced intracranial hypertension were collected. The expression level and distribution pattern of HMGB1, OX42 and NF‑κB p65 were detected by immunohistochemistry. HMGB1, TLR4, receptor for advanced glycation end products (RAGE), NF‑κB p65 and inducible nitric oxide synthase (iNOS) expression levels were detected by western blotting, and serum cytokine levels of interleukin (IL)‑1, IL‑6, tumor necrosis factor (TNF)‑α, transforming growth factor (TGF)‑β and IL‑10 in patients with epilepsy and craniocerebral trauma were detected by ELISA. And cell model of epilepsy was established by coriaria lactone (CL)‑stimulated HM cell, and the same factors were measured. The potential toxic effect of HMGB1 on HM cells was evaluated by MTT and 5‑ethynyl‑2‑deoxyuridine assays. The results demonstrated that compared with the control group, levels of HMGB1, TLR4, RAGE, NF‑κB p65 and iNOS in the brain of the epilepsy group were significantly increased, and increased cytokine levels of IL‑1, IL‑6, TNF‑α, TGF‑β and IL‑10 in patients with epilepsy were also observed. At the same time, the above results were also observed in HM cells stimulated with CL. Overexpression of HMGB1 enhanced the results, while HMGB1 small interfering RNA blocked the function of CL. There was no significant toxic effect of HMGB1 on HM cells. In conclusion, overexpression of HMGB1 potentially promoted epileptogenesis. CL‑induced activation of glial cells may act via up‑regulation of HMGB1 and TLR4/RAGE receptors, and the downstream transcription factor NF‑κB.

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