B7-H3 augments inflammatory responses and exacerbates brain damage via amplifying NF-κB p65 and MAPK p38 activation during experimental pneumococcal meningitis

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dc.contributor.author Chen, Xuqin
dc.contributor.author Li, Yan
dc.contributor.author Blankson, Siobhan
dc.contributor.author Liu, Min
dc.contributor.author Huang, Danping
dc.contributor.author Redmond, H. Paul
dc.contributor.author Huang, Jing
dc.contributor.author Wang, Jiang Huai
dc.contributor.author Wang, Jian
dc.date.accessioned 2017-03-06T17:49:11Z
dc.date.available 2017-03-06T17:49:11Z
dc.date.issued 2017-01-31
dc.identifier.citation Chen X., Li Y., Blankson S., Liu M., Huang D., Redmond H.P., Huang, J., Wang, J.H. and Wang, J. (2017) ‘B7-H3 augments inflammatory responses and exacerbates brain damage via amplifying NF-κB p65 and MAPK p38 activation during experimental pneumococcal meningitis’, PLoS ONE 12(1), e0171146 (16pp). doi:10.1371/journal.pone.0171146 en
dc.identifier.volume 12 en
dc.identifier.issued 1 en
dc.identifier.startpage 1 en
dc.identifier.endpage 16 en
dc.identifier.issn 1932-6203
dc.identifier.uri http://hdl.handle.net/10468/3749
dc.identifier.doi 10.1371/journal.pone.0171146
dc.description.abstract The costimulatory protein B7-H3 has been shown to play a contributory role in the development and progression of experimental pneumococcal meningitis by augmentation of the innate immunity-associated inflammatory response via a TLR2-dependent manner. This study aimed to clarify the component(s) of TLR2-mediated signal transduction pathways responsible for B7-H3-augmented inflammatory response and subsequent brain damage during experimental pneumococcal meningitis. Administration of B7-H3 did not augment expression of TLR2 and other TLR2 upstream components, but led to an enhanced formation of MyD88-IRAK immunocomplex in the brain of S. pneumoniae-infected mice. Furthermore, B7-H3 substantially augmented S. pneumoniae-induced activation of TLR2 downstream NF-κB p65 and MAPK p38 pathways in the brain of S. pneumoniae-infected mice. Notably, blockage of NF-κB p65 and/or MAPK p38 with their specific inhibitors strongly attenuated B7-H3-amplified inflammatory response with significantly reduced proinflammatory cytokine and chemokine production, and markedly ameliorated B7-H3-exacerbated disruption of bloodbrain barrier and severity of disease status in S. pneumoniae-infected mice. These results indicate that targeting NF-κB p65 and/or MAPK p38 may represent a promising therapeutic option for amelioration of overwhelming inflammatory response-associated brain injury frequently observed during pneumococcal meningitis. en
dc.description.sponsorship National Natural Science Foundation of China (Grants 81273242 and 81272143); Natural Science Foundation of Jiangsu Province (Grant BK20161227) en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher Public Library of Science en
dc.rights © 2017, the Authors. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. en
dc.rights.uri https://creativecommons.org/licenses/by/4.0/ en
dc.subject Pneumococcal en
dc.subject Meningitis en
dc.subject Inflammatory response en
dc.title B7-H3 augments inflammatory responses and exacerbates brain damage via amplifying NF-κB p65 and MAPK p38 activation during experimental pneumococcal meningitis en
dc.type Article (peer-reviewed) en
dc.internal.authorcontactother Henry Paul Redmond, Surgery, University College Cork, Cork, Ireland. +353-21-490-3000 Email: henry.redmond@hse.ie en
dc.internal.availability Full text available en
dc.date.updated 2017-03-03T13:33:33Z
dc.description.version Published Version en
dc.internal.rssid 385708942
dc.contributor.funder National Natural Science Foundation of China en
dc.contributor.funder Natural Science Foundation of Jiangsu Province en
dc.description.status Peer reviewed en
dc.identifier.journaltitle Plos ONE en
dc.internal.copyrightchecked Yes en
dc.internal.licenseacceptance Yes en
dc.internal.IRISemailaddress henry.redmond@hse.ie en
dc.identifier.articleid e0171146


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© 2017, the Authors. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Except where otherwise noted, this item's license is described as © 2017, the Authors. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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