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Treatment with a selective histone deacetylase 6 inhibitor decreases lupus nephritis in NZB/W mice

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dc.contributor.authorVieson, Miranda D.
dc.contributor.authorGojmerac, Alexander M.
dc.contributor.authorKhan, Deena
dc.contributor.authorDai, Rujuan
dc.contributor.authorvan Duzer, John H.
dc.contributor.authorMazitschek, Ralph
dc.contributor.authorCaudell, David L.
dc.contributor.authorLiao, Xiaofeng
dc.contributor.authorLuo, Xin M.
dc.contributor.authorReilly, Christopher M.
dc.date.accessioned2022-03-15T12:31:45Z
dc.date.available2022-03-15T12:31:45Z
dc.date.issued2017
dc.description.abstractTo date, there are 18 histone deacetylase (HDAC) enzymes, divided into four classes, which alter protein function by removing acetyl groups from lysine residues. Prior studies report that non-selective HDAC inhibitors decrease disease in lupus mouse models. Concern for adverse side effects of non-selective HDAC inhibition supports investigation of selective-HDAC inhibition. We hypothesized that a selective HDAC-6 inhibitor (HDAC6i) will alleviate disease in a mouse model of lupus by increasing acetylation of alphatubulin. Intraperitoneal injections of the selective HDAC6i ACY-1083 (0.3 mg/kg, 1 mg/kg, or 3 mg/kg), vehicle control, or dexamethasone were administered to 21-week-old, female NZB/W mice, 5 days a week, for 13 weeks. Disease progression was evaluated by proteinuria, serum levels of anti-dsDNA antibody, cytokines and immunoglobulins, and post mortem evaluation of nephritis and T cell populations in the spleen. HDAC6i treatment decreased proteinuria, glomerular histopathology, IgG, and C3 scores when compared to vehicle-treated mice. Within glomeruli of HDAC6i-treated mice, there was increased acetylation of alpha-tubulin and decreased NF-κB. Additionally, HDAC6i decreased serum IL-12/IL-23 and Th17 cells in the spleen. Taken together, these results suggest HDAC6 inhibition may decrease lupus nephritis in NZB/W mice via mechanisms involving acetylation of alphatubulin and decreased NF-κB in glomeruli as well as inhibition of Th17 cells.es
dc.formatapplication/pdfes
dc.format.extent16es
dc.identifier.citationHistology and Histopathology, Vol.32, nº12, (2017)
dc.identifier.doiDOI: 10.14670/HH-11-885
dc.identifier.issn1699-5848
dc.identifier.issn0213-3911
dc.identifier.urihttp://hdl.handle.net/10201/118008
dc.languageenges
dc.publisherUniversidad de Murcia. Departamento de Biología Celular e Histologíaes
dc.relationSin financiación externa a la Universidades
dc.rightsinfo:eu-repo/semantics/openAccesses
dc.rightsAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectLupuses
dc.subjectNephritises
dc.subjectHistone deacetylase inhibitores
dc.subjectAlpha-tubulines
dc.subject.otherCDU::6 - Ciencias aplicadas::61 - Medicina::616 - Patología. Medicina clínica. Oncologíaes
dc.titleTreatment with a selective histone deacetylase 6 inhibitor decreases lupus nephritis in NZB/W micees
dc.typeinfo:eu-repo/semantics/articlees
dspace.entity.typePublicationes
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Histology and histopathology Vol.32,nº12 (2017)