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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
Author(s) -
Lee Jaejoon,
Hong Eun Chung,
Jeong Hyemin,
Hwang Ji Won,
Kim Hyungjin,
Bae EunKyung,
Ahn Joong Kyong,
Choi YoonLa,
Han Jungho,
Cha HoonSuk,
Koh EunMi
Publication year - 2015
Publication title -
international journal of rheumatic diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.795
H-Index - 41
eISSN - 1756-185X
pISSN - 1756-1841
DOI - 10.1111/1756-185x.12501
Subject(s) - synovitis , medicine , arthritis , rheumatoid arthritis , inflammation , tumor necrosis factor alpha , pharmacology , pathology , immunology
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 ( FLS s) 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 FLS s 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.