Modulation of renal disease in MRL/lpr mice by suberoylanilide hydroxamic acid

Christopher M. Reilly, Nilamadhab Mishra, Julie M. Miller, Dimple Joshi, Phillip Ruiz, Victoria M. Richon, Paul A. Marks, Gary S. Gilkeson

Research output: Contribution to journalArticle

120 Citations (Scopus)

Abstract

Epigenetic regulation of gene expression is involved in the development of many diseases. Histone acetylation is a posttranslational modification of the nucleosomal histone tails that is regulated by the balance of histone deacetylases and histone acetyltransferases. Alterations in the balance of histone acetylation have been shown to cause aberrant expression of genes that are a hallmark of many diseases, including systemic lupus erythematosus. In this study, we determined whether suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor: 1) inhibits inflammatory mediator production in vitro and 2) modulates lupus progression in vivo. Mesangial cells isolated from 10-wk-old MRL/lpr mice were stimulated with LPS/IFN-γ and incubated with SAHA. TNF-α, IL-6, NO, and inducible NO synthase expression were inhibited by SAHA. We then treated MRL/lpr mice with daily injections of SAHA from age 10 to 20 wk. The animals treated with SAHA had decreased spleen size and a concomitant decrease in CD4-CD8- (double-negative) T cells compared with controls. Serum autoantibody levels and glomerular IgG and C3 deposition in SAHA-treated mice were similar to controls. In contrast, proteinuria and pathologic renal disease were significantly inhibited in the mice receiving SAHA. These data indicate that SAHA blocks mesangial cell inflammatory mediator production in vitro and disease progression in vivo in MRL/lpr mice.

Original languageEnglish
Pages (from-to)4171-4178
Number of pages8
JournalJournal of Immunology
Volume173
Issue number6
StatePublished - Sep 15 2004

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Inbred MRL lpr Mouse
Kidney
Histones
Mesangial Cells
Acetylation
Histone Deacetylase 1
Histone Acetyltransferases
Histone Deacetylase Inhibitors
Histone Deacetylases
vorinostat
Gene Expression Regulation
Post Translational Protein Processing
Proteinuria
Epigenomics
Nitric Oxide Synthase
Systemic Lupus Erythematosus
Autoantibodies
Disease Progression
Tail
Interleukin-6

ASJC Scopus subject areas

  • Immunology

Cite this

Reilly, C. M., Mishra, N., Miller, J. M., Joshi, D., Ruiz, P., Richon, V. M., ... Gilkeson, G. S. (2004). Modulation of renal disease in MRL/lpr mice by suberoylanilide hydroxamic acid. Journal of Immunology, 173(6), 4171-4178.

Modulation of renal disease in MRL/lpr mice by suberoylanilide hydroxamic acid. / Reilly, Christopher M.; Mishra, Nilamadhab; Miller, Julie M.; Joshi, Dimple; Ruiz, Phillip; Richon, Victoria M.; Marks, Paul A.; Gilkeson, Gary S.

In: Journal of Immunology, Vol. 173, No. 6, 15.09.2004, p. 4171-4178.

Research output: Contribution to journalArticle

Reilly, CM, Mishra, N, Miller, JM, Joshi, D, Ruiz, P, Richon, VM, Marks, PA & Gilkeson, GS 2004, 'Modulation of renal disease in MRL/lpr mice by suberoylanilide hydroxamic acid', Journal of Immunology, vol. 173, no. 6, pp. 4171-4178.
Reilly CM, Mishra N, Miller JM, Joshi D, Ruiz P, Richon VM et al. Modulation of renal disease in MRL/lpr mice by suberoylanilide hydroxamic acid. Journal of Immunology. 2004 Sep 15;173(6):4171-4178.
Reilly, Christopher M. ; Mishra, Nilamadhab ; Miller, Julie M. ; Joshi, Dimple ; Ruiz, Phillip ; Richon, Victoria M. ; Marks, Paul A. ; Gilkeson, Gary S. / Modulation of renal disease in MRL/lpr mice by suberoylanilide hydroxamic acid. In: Journal of Immunology. 2004 ; Vol. 173, No. 6. pp. 4171-4178.
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