1. A novel histone deacetylase 6-selective inhibitor suppresses synovial inflammation and joint destruction in a collagen antibody-induced arthritis mouse model.
- Author
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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, and Koh, Eun‐Mi
- Subjects
HISTONE deacetylase inhibitors ,SYNOVITIS ,ARTHRITIS in animals ,ANIMAL disease models ,ENZYME-linked immunosorbent assay ,COMPUTED tomography - 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]
- Published
- 2015
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