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Therapeutic potential of CKD-506, a novel selective histone deacetylase 6 inhibitor, in a murine model of rheumatoid arthritis
DC Field | Value | Language |
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dc.contributor.author | Park, Jin K | - |
dc.contributor.author | Jang, Yu J | - |
dc.contributor.author | Oh, Bo R | - |
dc.contributor.author | Shin, Jieun | - |
dc.contributor.author | Bae, Daekwon | - |
dc.contributor.author | Ha, Nina | - |
dc.contributor.author | Choi, Young i | - |
dc.contributor.author | Youn, Gi S | - |
dc.contributor.author | Park, Jinseu | - |
dc.contributor.author | Lee, Eun Y | - |
dc.contributor.author | Lee, Eun B | - |
dc.contributor.author | Song, Yeong W | - |
dc.date.accessioned | 2020-09-09T05:27:08Z | - |
dc.date.available | 2020-09-09T05:27:08Z | - |
dc.date.issued | 2020-07-25 | - |
dc.identifier.citation | Arthritis Research & Therapy. 2020 Jul 25;22(1):176 | - |
dc.identifier.uri | https://doi.org/10.1186/s13075-020-02258-0 | - |
dc.identifier.uri | https://hdl.handle.net/10371/168854 | - |
dc.description.abstract | Abstract
Objectives Histone deacetylase (HDAC) 6 promotes inflammation. We investigated the anti-arthritic effects of CKD-506, a novel HDAC6 inhibitor, in vitro and in a murine model of arthritis as a novel treatment option for rheumatoid arthritis (RA). Methods HDAC6 was overexpressed in mouse peritoneal macrophages and RAW 264.7 cells, and the effects of a HDAC6 inhibitor CKD-506 on cytokine production and activity of NF-κB and AP-1 signaling were examined. Peripheral blood mononuclear cells (PBMCs) from RA patients and fibroblast-like synoviocytes (FLS) were activated in the presence of CKD-506. Next, regulatory T cells (Tregs) were induced from RA patients and co-cultured with healthy effector T cells (Teffs) and cell proliferation was analyzed by flow cytometry. Finally, the effects of the inhibitor on the severity of arthritis were assessed in a murine model of adjuvant-induced arthritis (AIA). Results Overexpression of HDAC6 induced macrophages to produce TNF-α and IL-6. The inhibitory effect of CKD-506 was mediated via blockade of NF-κB and AP-1 activation. HDAC6 inhibition reduced TNF-α and IL-6 production by activated RA PBMCs. CKD-506 inhibited production of MMP-1, MMP-3, IL-6, and IL-8 by activated FLS. In addition, CKD-506 inhibited proliferation of Teffs directly and indirectly by improving iTreg function. In AIA rats, oral CKD-506 improved clinical arthritis in a dose-dependent manner. A combination of sub-therapeutic CKD-506 and methotrexate exerted a synergistic effect. Conclusion The novel HDAC6 inhibitor CKD-506 suppresses inflammatoryresponses by monocytes/macrophages, improves Treg function, and ameliorates arthritis severity in a murine model of RA. Thus, CKD-506 might be a novel and effective treatment option for RA. | - |
dc.title | Therapeutic potential of CKD-506, a novel selective histone deacetylase 6 inhibitor, in a murine model of rheumatoid arthritis | - |
dc.type | Journal Article | - |
dc.language.rfc3066 | en | - |
dc.rights.holder | The Author(s) | - |
dc.date.updated | 2020-07-26T03:55:44Z | - |
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