open access

Vol 78, No 1 (2019)
ORIGINAL ARTICLES
Published online: 2018-07-17
Submitted: 2018-06-27
Accepted: 2018-07-16
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High-mobility group box 1, an endogenous ligand of toll-like receptors 2 and 4, induces astroglial inflammation via nuclear factor kappa B pathway

E. A. Al-ofi, B. S. Al-Ghamdi
DOI: 10.5603/FM.a2018.0068
·
Pubmed: 30106464
·
Folia Morphol 2019;78(1):10-16.

open access

Vol 78, No 1 (2019)
ORIGINAL ARTICLES
Published online: 2018-07-17
Submitted: 2018-06-27
Accepted: 2018-07-16

Abstract

Background: Neuroinflammation has a definitive role in neurodegenerative diseases, such as Parkinson’s and Alzheimer’s disease. In addition to its pathoge- nic 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 un- treated 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 me- chanisms 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. 

Abstract

Background: Neuroinflammation has a definitive role in neurodegenerative diseases, such as Parkinson’s and Alzheimer’s disease. In addition to its pathoge- nic 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 un- treated 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 me- chanisms 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. 

Get Citation

Keywords

toll-like receptors; immunohistochemistry; signalling pathway; high-mobility group box 1

About this article
Title

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

Journal

Folia Morphologica

Issue

Vol 78, No 1 (2019)

Pages

10-16

Published online

2018-07-17

DOI

10.5603/FM.a2018.0068

Pubmed

30106464

Bibliographic record

Folia Morphol 2019;78(1):10-16.

Keywords

toll-like receptors
immunohistochemistry
signalling pathway
high-mobility group box 1

Authors

E. A. Al-ofi
B. S. Al-Ghamdi

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