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2019 | 78 | 1 |

Tytuł artykułu

High-mobility group box 1, an endogenous ligand of toll-like receptors 2 and 4, induces astroglial inflammation via nuclear factor kappa B pathway

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Background: Neuroinflammation has a definitive role in neurodegenerative diseases, such as Parkinson’s and Alzheimer’s disease. In addition to its pathogenic ligands, toll-like receptors (TLRs) can be activated by damaged endogenous molecules that induce inflammatory signalling pathways such as high-mobility group box 1 protein (HMGB1). Materials and methods: Using an ex-vivo rat optic nerve (RON) model, we sought to determine the effects of lipopolysaccharides (LPS; TLR4 agonist), zymosan (TLR2 agonist) or HMGB1 — with or without TLR2/4 antagonists, on the expression of glial fibrillary acidic protein (GFAP) and nuclear factor kappa B (NF-ҡβ) for signalling pathway and astrocyte reactivity, using double immunohistochemistry; as well as on the modulation of the neurotoxicity. HMGB1-treated RON had significantly higher expression and co-localisation of GFAP and NF-ҡβ as compared to the untreated control, which was a similar result to those treated with LPS and zymosan. Results: Moreover, the HMGB1-induced inflammation was blocked by TLR2/4 antagonists (p = 0.05). However, the HMGB1-induced cell death was unblocked by TLR antagonists. Overall, HMGB1 endogenously mediates the signalling mechanisms of neuroinflammation through TLR2/4. Conclusions: Whereas, the neuronal death mechanism resulting from HMGB1 could be caused by a different signalling pathway. Gaining an understanding of these mechanisms may help researchers discover new therapeutic targets for neurodegenerative diseases. (Folia Morphol 2018; 78, 1: 10–16)

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  • Department of Physiology and Neuroscience Research Unit, Faculty of Medicine, King Abdulaziz University, Branch of Sulaymaniyah, Jeddah 21589, Saudi Arabia
  • Neuroscience Research Unit, King Abdulaziz University, Faculty of Medicine, Branch of Sulaymaniyah, Jeddah, Saudi Arabia
  • Department of Physiology and Neuroscience Research Unit, Faculty of Medicine, King Abdulaziz University, Branch of Sulaymaniyah, Jeddah 21589, Saudi Arabia
  • Neuroscience Research Unit, King Abdulaziz University, Faculty of Medicine, Branch of Sulaymaniyah, Jeddah, Saudi Arabia


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