Disulfide HMGB1 acts via TLR2/4 receptors to reduce the numbers of oligodendrocyte progenitor cells after traumatic injury in vitro

Abstract Traumatic brain injury (TBI) is associated with poor clinical outcomes; autopsy studies of TBI victims demonstrate significant oligodendrocyte progenitor cell (OPC) death post TBI; an observation, which may explain the lack of meaningful repair of injured axons. Whilst high-mobility group b...

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Autores principales:	R. Ved, F. Sharouf, B. Harari, M. Muzaffar, S. Manivannan, C. Ormonde, W. P. Gray, M. Zaben
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/84c6f53091dd46c88e22c6d49e403648
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spelling	oai:doaj.org-article:84c6f53091dd46c88e22c6d49e4036482021-12-02T17:04:53ZDisulfide HMGB1 acts via TLR2/4 receptors to reduce the numbers of oligodendrocyte progenitor cells after traumatic injury in vitro10.1038/s41598-021-84932-02045-2322https://doaj.org/article/84c6f53091dd46c88e22c6d49e4036482021-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-84932-0https://doaj.org/toc/2045-2322Abstract Traumatic brain injury (TBI) is associated with poor clinical outcomes; autopsy studies of TBI victims demonstrate significant oligodendrocyte progenitor cell (OPC) death post TBI; an observation, which may explain the lack of meaningful repair of injured axons. Whilst high-mobility group box-1 (HMGB1) and its key receptors TLR2/4 are identified as key initiators of neuroinflammation post-TBI, they have been identified as attractive targets for development of novel therapeutic approaches to improve post-TBI clinical outcomes. In this report we establish unequivocal evidence that HMGB1 released in vitro impairs OPC response to mechanical injury; an effect that is pharmacologically reversible. We show that needle scratch injury hyper-acutely induced microglial HMGB1 nucleus-to-cytoplasm translocation and subsequent release into culture medium. Application of injury-conditioned media resulted in significant decreases in OPC number through anti-proliferative effects. This effect was reversed by co-treatment with the TLR2/4 receptor antagonist BoxA. Furthermore, whilst injury conditioned medium drove OPCs towards an activated reactive morphology, this was also abolished after BoxA co-treatment. We conclude that HMGB1, through TLR2/4 dependant mechanisms, may be detrimental to OPC proliferation following injury in vitro, negatively affecting the potential for restoring a mature oligodendrocyte population, and subsequent axonal remyelination. Further study is required to assess how HMGB1-TLR signalling influences OPC maturation and myelination capacity.R. VedF. SharoufB. HarariM. MuzaffarS. ManivannanC. OrmondeW. P. GrayM. ZabenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q R. Ved F. Sharouf B. Harari M. Muzaffar S. Manivannan C. Ormonde W. P. Gray M. Zaben Disulfide HMGB1 acts via TLR2/4 receptors to reduce the numbers of oligodendrocyte progenitor cells after traumatic injury in vitro
description	Abstract Traumatic brain injury (TBI) is associated with poor clinical outcomes; autopsy studies of TBI victims demonstrate significant oligodendrocyte progenitor cell (OPC) death post TBI; an observation, which may explain the lack of meaningful repair of injured axons. Whilst high-mobility group box-1 (HMGB1) and its key receptors TLR2/4 are identified as key initiators of neuroinflammation post-TBI, they have been identified as attractive targets for development of novel therapeutic approaches to improve post-TBI clinical outcomes. In this report we establish unequivocal evidence that HMGB1 released in vitro impairs OPC response to mechanical injury; an effect that is pharmacologically reversible. We show that needle scratch injury hyper-acutely induced microglial HMGB1 nucleus-to-cytoplasm translocation and subsequent release into culture medium. Application of injury-conditioned media resulted in significant decreases in OPC number through anti-proliferative effects. This effect was reversed by co-treatment with the TLR2/4 receptor antagonist BoxA. Furthermore, whilst injury conditioned medium drove OPCs towards an activated reactive morphology, this was also abolished after BoxA co-treatment. We conclude that HMGB1, through TLR2/4 dependant mechanisms, may be detrimental to OPC proliferation following injury in vitro, negatively affecting the potential for restoring a mature oligodendrocyte population, and subsequent axonal remyelination. Further study is required to assess how HMGB1-TLR signalling influences OPC maturation and myelination capacity.
format	article
author	R. Ved F. Sharouf B. Harari M. Muzaffar S. Manivannan C. Ormonde W. P. Gray M. Zaben
author_facet	R. Ved F. Sharouf B. Harari M. Muzaffar S. Manivannan C. Ormonde W. P. Gray M. Zaben
author_sort	R. Ved
title	Disulfide HMGB1 acts via TLR2/4 receptors to reduce the numbers of oligodendrocyte progenitor cells after traumatic injury in vitro
title_short	Disulfide HMGB1 acts via TLR2/4 receptors to reduce the numbers of oligodendrocyte progenitor cells after traumatic injury in vitro
title_full	Disulfide HMGB1 acts via TLR2/4 receptors to reduce the numbers of oligodendrocyte progenitor cells after traumatic injury in vitro
title_fullStr	Disulfide HMGB1 acts via TLR2/4 receptors to reduce the numbers of oligodendrocyte progenitor cells after traumatic injury in vitro
title_full_unstemmed	Disulfide HMGB1 acts via TLR2/4 receptors to reduce the numbers of oligodendrocyte progenitor cells after traumatic injury in vitro
title_sort	disulfide hmgb1 acts via tlr2/4 receptors to reduce the numbers of oligodendrocyte progenitor cells after traumatic injury in vitro
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/84c6f53091dd46c88e22c6d49e403648
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Disulfide HMGB1 acts via TLR2/4 receptors to reduce the numbers of oligodendrocyte progenitor cells after traumatic injury in vitro

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