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http://purl.uniprot.org/citations/23206318http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
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Background

Innate immune gene expression is regulated in part through high mobility group box 1 (HMGB1), an endogenous proinflammatory cytokine, that activates multiple members of the interleukin-1/Toll-like receptor (TLR) family associated with danger signaling. We investigated expression of HMGB1, TLR2, TLR3, and TLR4 in chronic ethanol-treated mouse brain, postmortem human alcoholic brain, and rat brain slice culture to test the hypothesis that neuroimmune activation in alcoholic brain involves ethanol activation of HMGB1/TLR danger signaling.

Methods

Protein levels were assessed using Western blot, enzyme-linked immunosorbent assay, and immunohistochemical immunoreactivity (+IR), and messenger RNA (mRNA) levels were measured by real time polymerase chain reaction in ethanol-treated mice (5 g/kg/day, intragastric, 10 days + 24 hours), rat brain slice culture, and postmortem human alcoholic brain.

Results

Ethanol treatment of mice increased brain mRNA and +IR protein expression of HMGB1, TLR2, TLR3, and TLR4. Postmortem human alcoholic brain also showed increased HMGB1, TLR2, TLR3, and TLR4 +IR cells that correlated with lifetime alcohol consumption, as well as each other. Ethanol treatment of brain slice culture released HMGB1 into the media and induced the proinflammatory cytokine, interleukin-1 beta (IL-1β). Neutralizing antibodies to HMGB1 and small inhibitory mRNA to HMGB1 or TLR4 blunted ethanol induction of IL-1β.

Conclusions

Ethanol-induced HMGB1/TLR signaling contributes to induction of the proinflammatory cytokine, IL-1β. Increased expression of HMGB1, TLR2, TLR3, and TLR4 in alcoholic brain and in mice treated with ethanol suggests that chronic alcohol-induced brain neuroimmune activation occurs through HMGB1/TLR signaling."xsd:string
http://purl.uniprot.org/citations/23206318http://purl.org/dc/terms/identifier"doi:10.1016/j.biopsych.2012.09.030"xsd:string
http://purl.uniprot.org/citations/23206318http://purl.uniprot.org/core/author"Zou J."xsd:string
http://purl.uniprot.org/citations/23206318http://purl.uniprot.org/core/author"Qin L."xsd:string
http://purl.uniprot.org/citations/23206318http://purl.uniprot.org/core/author"Crews F.T."xsd:string
http://purl.uniprot.org/citations/23206318http://purl.uniprot.org/core/author"Sheedy D."xsd:string
http://purl.uniprot.org/citations/23206318http://purl.uniprot.org/core/author"Vetreno R.P."xsd:string
http://purl.uniprot.org/citations/23206318http://purl.uniprot.org/core/date"2013"xsd:gYear
http://purl.uniprot.org/citations/23206318http://purl.uniprot.org/core/name"Biol Psychiatry"xsd:string
http://purl.uniprot.org/citations/23206318http://purl.uniprot.org/core/pages"602-612"xsd:string
http://purl.uniprot.org/citations/23206318http://purl.uniprot.org/core/title"High mobility group box 1/Toll-like receptor danger signaling increases brain neuroimmune activation in alcohol dependence."xsd:string
http://purl.uniprot.org/citations/23206318http://purl.uniprot.org/core/volume"73"xsd:string
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