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A novel histone deacetylase 6-selective inhibitor suppresses synovial inflammation and joint destruction in a collagen antibody-induced arthritis mouse model.

Authors :
Lee, Jaejoon
Hong, Eun Chung
Jeong, Hyemin
Hwang, Ji Won
Kim, Hyungjin
Bae, Eun‐Kyung
Ahn, Joong Kyong
Choi, Yoon‐La
Han, Jungho
Cha, Hoon‐Suk
Koh, Eun‐Mi
Source :
International Journal of Rheumatic Diseases; Jun2015, Vol. 18 Issue 5, p514-523, 10p
Publication Year :
2015

Abstract

Aim To investigate the effects of Tubastatin A, a selective histone deacetylase-6 inhibitor, on synovial inflammation and joint destruction in a collagen antibody-induced arthritis ( CAIA) mouse model. Methods Collagen antibody-induced arthritis mice were given daily intraperitoneal injections of various concentrations of Tubastatin A (0, 10, 50, 100 mg/kg). The clinical score and paw thickness were measured. Mice were sacrificed on day 15, and the expression of tumor necrosis factor ( TNF)-α, interleukin ( IL)-1 and IL-6 in the serum were analyzed using enyme-linked immunosorbent assay ( ELISA). Two pathologists independently measured the synovitis score. Micro-computed tomography ( CT) scans of the joints were performed to quantify joint destruction. The expression of IL-6 from human fibroblast-like synoviocytes ( FLSs) after incubation with various doses of Tubastatin A (0, 0.75, 1.5, 3 μmol/L) was measured using ELISA. Results The clinical arthritis score was significantly attenuated and paw thickness was lower in the group treated with 100 mg/kg Tubastatin A compared with those treated with vehicle alone. The synovitis score was significantly reduced in the 100 mg/kg Tubastatin A-treated group compared with the control group. Micro- CT showed that quantitative measures of joint destruction were significantly attenuated in the 100 mg/kg Tubastatin A-treated group compared with the control. The expression of IL-6 in the sera was lower in the mice treated with Tubastatin A compared with the control. The expression of IL-6 in human FLSs decreased dose-dependently after incubation with Tubastatin A without affecting cell viability. Conclusions Tubastatin A successfully ameliorated synovial inflammation and protected against joint destruction in CAIA mice, at least in part, by modulating IL-6 expression. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
17561841
Volume :
18
Issue :
5
Database :
Complementary Index
Journal :
International Journal of Rheumatic Diseases
Publication Type :
Academic Journal
Accession number :
103265334
Full Text :
https://doi.org/10.1111/1756-185X.12501