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.authorChen, Xuqin
dc.contributor.authorLi, Yan
dc.contributor.authorBlankson, Siobhan
dc.contributor.authorLiu, Min
dc.contributor.authorHuang, Danping
dc.contributor.authorRedmond, H. Paul
dc.contributor.authorHuang, Jing
dc.contributor.authorWang, Jiang Huai
dc.contributor.authorWang, Jian
dc.contributor.funderNational Natural Science Foundation of Chinaen
dc.contributor.funderNatural Science Foundation of Jiangsu Provinceen
dc.date.accessioned2017-03-06T17:49:11Z
dc.date.available2017-03-06T17:49:11Z
dc.date.issued2017-01-31
dc.date.updated2017-03-03T13:33:33Z
dc.description.abstractThe 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.sponsorshipNational Natural Science Foundation of China (Grants 81273242 and 81272143); Natural Science Foundation of Jiangsu Province (Grant BK20161227)en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.articleide0171146
dc.identifier.citationChen 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.0171146en
dc.identifier.doi10.1371/journal.pone.0171146
dc.identifier.endpage16en
dc.identifier.issn1932-6203
dc.identifier.issued1en
dc.identifier.journaltitlePlos ONEen
dc.identifier.startpage1en
dc.identifier.urihttps://hdl.handle.net/10468/3749
dc.identifier.volume12en
dc.language.isoenen
dc.publisherPublic Library of Scienceen
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.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subjectPneumococcalen
dc.subjectMeningitisen
dc.subjectInflammatory responseen
dc.titleB7-H3 augments inflammatory responses and exacerbates brain damage via amplifying NF-κB p65 and MAPK p38 activation during experimental pneumococcal meningitisen
dc.typeArticle (peer-reviewed)en
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