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

作者：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^*

来源：International Journal of Rheumatic Diseases, 2015, 18(5): 514-523.

DOI：10.1111/1756-185X.12501

• rheumatoid arthritis
• tubastatin
• erosion
• collagen antibody-induced arthritis

AimTo 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.
MethodsCollagen antibody-induced arthritis mice were given daily intraperitoneal injections of various concentrations of Tubastatin A (0, 10, 50, 100mg/kg). The clinical score and paw thickness were measured. Mice were sacrificed on day 15, and the expression of tumor necrosis factor (TNF)-, 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, 3mol/L) was measured using ELISA.
ResultsThe clinical arthritis score was significantly attenuated and paw thickness was lower in the group treated with 100mg/kg Tubastatin A compared with those treated with vehicle alone. The synovitis score was significantly reduced in the 100mg/kg Tubastatin A-treated group compared with the control group. Micro-CT showed that quantitative measures of joint destruction were significantly attenuated in the 100mg/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.
ConclusionsTubastatin A successfully ameliorated synovial inflammation and protected against joint destruction in CAIA mice, at least in part, by modulating IL-6 expression.

• 出版日期2015-6