Specific HDAC6 inhibition by ACY-738 reduces SLE pathogenesis in NZB/W mice

Specific HDAC6 inhibition by ACY-738 reduces SLE pathogenesis in NZB/W mice

Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Bibliographische Detailangaben
Veröffentlicht in:Clinical immunology (Orlando, Fla.). - 1999. - 162(2016) vom: 25. Jan., Seite 58-73
1. Verfasser: Regna, Nicole L (VerfasserIn)
Weitere Verfasser: Vieson, Miranda D, Luo, Xin M, Chafin, Cristen B, Puthiyaveetil, Abdul Gafoor, Hammond, Sarah E, Caudell, David L, Jarpe, Matthew B, Reilly, Christopher M
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2016
Zugriff auf das übergeordnete Werk:Clinical immunology (Orlando, Fla.)
Schlagworte:Journal Article Research Support, Non-U.S. Gov't B cells HDAC Systemic lupus erythematosus T cells Enzyme Inhibitors Hydroxamic Acids N-hydroxy-2-(1-phenylcycloproylamino)pyrimidine-5-carboxamide Pyrimidines mehr... Hdac6 protein, mouse EC 3.5.1.98 Histone Deacetylase 6 Histone Deacetylases
Beschreibung
Zusammenfassung:Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.
We sought to determine if a selective HDAC6 inhibitor (ACY-738) decreases disease in NZB/W mice. From 22 to 38weeks-of-age, mice were injected intraperitoneally with 5 or 20mg/kg of ACY-738, or vehicle control. Body weight and proteinuria were measured every 2weeks, while sera anti-dsDNA, Ig isotypes, and cytokine levels were measured every 4weeks. Kidney disease was determined by evaluation of sera, urine, immune complex deposition, and renal pathology. Flow cytometric analysis assessed thymic, splenic, bone marrow, and peripheral lymphocyte differentiation patterns. Our results showed HDAC6 inhibition decreased SLE disease by inhibiting immune complex-mediated glomerulonephritis, sera anti-dsDNA levels, and inflammatory cytokine production and increasing splenic Treg cells. Inhibition of HDAC6 increased the percentage of cells in the early-stage developmental fractions of both pro- and pre-B cells. These results suggest that specific HDAC6 inhibition may be able to decrease SLE disease by altering aberrant T and B cell differentiation
Beschreibung:Date Completed 05.05.2016
Date Revised 16.11.2017
published: Print-Electronic
Citation Status MEDLINE
ISSN:1521-7035
DOI:10.1016/j.clim.2015.11.007