A novel histone deacetylase 6‐selective inhibitor suppresses synovial inflammation and joint destruction in a collagen antibody‐induced arthritis mouse model. (20th December 2014)

• Record Type: Journal Article
• 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
• Is Part Of: International journal of rheumatic diseases. Volume 18:Number 5(2015)
• Page Start: 514
• Page End: 523
• Publication Date: 2014-12-20
• Subjects: Rheumatology -- Periodicals; Rheumatology -- Asia -- Periodicals; Rheumatology -- Pacific Area -- Periodicals; Rheumatic Diseases -- Periodicals; Connective Tissue Diseases -- Periodicals; Immune System Diseases -- Periodicals; 616.723
• DOI: 10.1111/1756-185X.12501
• Languages: English
• ISSNs: 1756-1841

Abstract

<abstract abstract-type="main" id="apl12501-abs-0001"> <title>Abstract</title> <sec id="apl12501-sec-0001" sec-type="section"> <title>Aim</title> <p>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.</p> </sec> <sec id="apl12501-sec-0002" sec-type="section"> <title>Methods</title> <p>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.</p> </sec> <sec id="apl12501-sec-0003" sec-type="section"> <title>Results</title> <p>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.</p> </sec> <sec id="apl12501-sec-0004" sec-type="section"> <title>Conclusions</title> <p>Tubastatin A successfully ameliorated synovial inflammation and protected against joint destruction in CAIA mice, at least in part, by modulating IL‐6 expression.</p> </sec> </abstract>