Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
Background/Purpose: Rheumatoid Arthritis (RA) is a chronic inflammatory autoimmune disease whose etiology is unclear. Recently, upregulated HDAC (histone deacetylase) activity has been reported in peripheral blood mononuclear cell (PBMC) from RA patient. In addition, it was reported that HDAC6 inhibitor (HDAC6i) improves cancers and inflammatory diseases by suppressing cell migration and proliferation and reducing pro-inflammatory cytokines such as TNF-α. Here, we investigated the therapeutic effects of a new HDAC6 inhibitor, CKD-M808 (M808), specifically targeting catalytic domain 1 of HDAC6 in RA.
Methods: We made adjuvant induced arthritis (AIA) model by injection of complete Freund’s adjuvant (CFA) subcutaneously into the tail base of Lewis rat on the 1st day of experiment. Vehicle (n=9) and M808 (10, 30, 50 and 100 mg/kg, n=9, 9, 8 and 10, respectively) were administered orally every day. Clinical score was measured at 10th, 14th and 17th days after induction. PBMC from RA patients were treated with HDAC6i (Tubastatin A and M808) for 24 hours under lipopolysaccharide (LPS) stimulation. After incubation, cell viability and the levels of cytokines including TNF-α, IL-1ß, IL-6 and IL-10 in culture supernatant were measured using CCK-8 and multiplex ELISA assay, respectively. Fibroblast-like synoviocyte (FLS) from RA patients were treated with HDAC6i for 24 hours under IL-1ß stimulation. The levels of IL-6, MMP-1 and MMP-3 were measured in culture supernatant. Cortactin and acetylated cortactin in HDAC6i-treated RA-FLS were measured by Western blotting.
To cite this abstract in AMA style:Shon S, Park JS, Bae D, Ha N, Choi YI, Park JK, Lee EY, Lee EB, Song YW. Therapeutic Role of a Novel Histone Deacetylase 6 Inhibitor, CKD-M808, in Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/therapeutic-role-of-a-novel-histone-deacetylase-6-inhibitor-ckd-m808-in-rheumatoid-arthritis/. Accessed March 7, 2021.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/therapeutic-role-of-a-novel-histone-deacetylase-6-inhibitor-ckd-m808-in-rheumatoid-arthritis/