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dc.contributor.authorDukay, Brigitta
dc.contributor.authorWalter, Fruzsina
dc.contributor.authorVigh, Judit
dc.contributor.authorBarabasi, Beata
dc.contributor.authorHajdu, Petra
dc.contributor.authorBalassa, Tamas
dc.contributor.authorMigh, Ede
dc.contributor.authorKincses, Andras
dc.contributor.authorHoyk, Zsofia
dc.contributor.authorSzogi, Titanilla
dc.contributor.authorBorbely, Emoke
dc.contributor.authorCsoboz, Balint
dc.contributor.authorHorvath, Peter
dc.contributor.authorFulop, Livia
dc.contributor.authorPenke, Botond
dc.contributor.authorVigh, Laszlo
dc.contributor.authorDeli, Maria
dc.contributor.authorSantha, Mikos
dc.contributor.authorToth, Melinda
dc.date.accessioned2021-07-05T08:16:18Z
dc.date.available2021-07-05T08:16:18Z
dc.date.issued2021-01-10
dc.description.abstractBackground - Heat-shock protein B1 (HSPB1) is among the most well-known and versatile member of the evolutionarily conserved family of small heat-shock proteins. It has been implicated to serve a neuroprotective role against various neurological disorders via its modulatory activity on inflammation, yet its exact role in neuroinflammation is poorly understood. In order to shed light on the exact mechanism of inflammation modulation by HSPB1, we investigated the effect of HSPB1 on neuroinflammatory processes in an in vivo and in vitro model of acute brain injury.<p> <p>Methods - In this study, we used a transgenic mouse strain overexpressing the human HSPB1 protein. In the in vivo experiments, 7-day-old transgenic and wild-type mice were treated with ethanol. Apoptotic cells were detected using TUNEL assay. The mRNA and protein levels of cytokines and glial cell markers were examined using RT-PCR and immunohistochemistry in the brain. We also established primary neuronal, astrocyte, and microglial cultures which were subjected to cytokine and ethanol treatments. TNFα and hHSPB1 levels were measured from the supernates by ELISA, and intracellular hHSPB1 expression was analyzed using fluorescent immunohistochemistry.<p> <p>Results - Following ethanol treatment, the brains of hHSPB1-overexpressing mice showed a significantly higher mRNA level of pro-inflammatory cytokines (Tnf, Il1b), microglia (Cd68, Arg1), and astrocyte (Gfap) markers compared to wild-type brains. Microglial activation, and 1 week later, reactive astrogliosis was higher in certain brain areas of ethanol-treated transgenic mice compared to those of wild-types. Despite the remarkably high expression of pro-apoptotic Tnf, hHSPB1-overexpressing mice did not exhibit higher level of apoptosis. Our data suggest that intracellular hHSPB1, showing the highest level in primary astrocytes, was responsible for the inflammation-regulating effects. Microglia cells were the main source of TNFα in our model. Microglia isolated from hHSPB1-overexpressing mice showed a significantly higher release of TNFα compared to wild-type cells under inflammatory conditions.<p> <p>Conclusions</i> - Our work provides novel in vivo evidence that hHSPB1 overexpression has a regulating effect on acute neuroinflammation by intensifying the expression of pro-inflammatory cytokines and enhancing glial cell activation, but not increasing neuronal apoptosis. These results suggest that hHSPB1 may play a complex role in the modulation of the ethanol-induced neuroinflammatory response.en_US
dc.identifier.citationDukay, Walter, Vigh, Barabasi, Hajdu, Balassa, Migh, Kincses, Hoyk, Szogi, Borbely, Csoboz, Horvath, Fulop, Penke, Vigh, Deli, Santha, Toth. Neuroinflammatory processes are augmented in mice overexpressing human heat-shock protein B1 following ethanol-induced brain injury. Journal of Neuroinflammation. 2021
dc.identifier.cristinIDFRIDAID 1901418
dc.identifier.doi10.1186/s12974-020-02070-2
dc.identifier.issn1742-2094
dc.identifier.urihttps://hdl.handle.net/10037/21717
dc.language.isoengen_US
dc.publisherBMCen_US
dc.relation.journalJournal of Neuroinflammation
dc.rights.holderCopyright 2021 The Author(s)en_US
dc.subjectVDP::Medical disciplines: 700::Basic medical, dental and veterinary science disciplines: 710en_US
dc.subjectVDP::Medisinske Fag: 700::Basale medisinske, odontologiske og veterinærmedisinske fag: 710en_US
dc.titleNeuroinflammatory processes are augmented in mice overexpressing human heat-shock protein B1 following ethanol-induced brain injuryen_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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