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

Miranda D. Vieson, Alexander M. Gojmerac, Deena Khan, Rujuan Dai, John H. van Duzer, Ralph Mazitschek, David L. Caudell, Xiaofeng Liao, Xin M. Luo, Christopher M. Reilly

Research output: Contribution to journalArticlepeer-review


To 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 HDAC- 6 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.

Original languageEnglish (US)
Pages (from-to)1317-1332
Number of pages16
JournalHistology and Histopathology
Issue number12
StatePublished - Dec 2017
Externally publishedYes


  • Alpha-tubulin
  • Histone deacetylase inhibitor
  • Lupus
  • Nephritis

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology


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