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Therapeutic effect of a novel histone deacetylase 6 inhibitor, CKD-L, on collagen-induced arthritis in vivo and regulatory T cells in rheumatoid arthritis in vitro
DC Field | Value | Language |
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dc.contributor.author | Oh, Bo Ram | - |
dc.contributor.author | Suh, Dong-hyeon | - |
dc.contributor.author | Bae, Daekwon | - |
dc.contributor.author | Ha, Nina | - |
dc.contributor.author | Choi, Young Il | - |
dc.contributor.author | Yoo, Hyun Jung | - |
dc.contributor.author | Park, Jin Kyun | - |
dc.contributor.author | Lee, Eun Young | - |
dc.contributor.author | Lee, Eun Bong | - |
dc.contributor.author | Song, Yeong Wook | - |
dc.date.accessioned | 2017-07-11T06:27:59Z | - |
dc.date.available | 2017-07-24T11:45:24Z | - |
dc.date.issued | 2017-07-03 | - |
dc.identifier.citation | Arthritis Research & Therapy. 2017 Jul 03;19(1):154 | - |
dc.identifier.issn | 1478-6362 | - |
dc.identifier.uri | 10.1186/s13075-017-1357-2 | - |
dc.identifier.uri | https://hdl.handle.net/10371/117781 | - |
dc.description.abstract | Background
Histone deacetylase (HDAC) inhibitor has recently been reported to have a therapeutic effect as an anti-inflammatory agent in collagen-induced arthritis (CIA). We investigated the therapeutic effect of a new selective HDAC6 inhibitor, CKD-L, compared to ITF 2357 or Tubastatin A on CIA and regulatory T (Treg) cells in patients with rheumatoid arthritis (RA). Methods CIA was induced by bovine type II collagen (CII) in DBA/1J mice. Mice were treated with HDAC inhibitor for 18days. Arthritis score was assessed and histological analysis was performed by hematoxylin and eosin (H&E) stain. Cytotoxic T-lymphocyte associated protein (CTLA)-4 expression in induced Treg cells was analyzed and suppression assay was analyzed using Treg cells and effector T (Teff) cells isolated from naive C57BL/6 mice by flow cytometry. Cytokines were analyzed in peripheral blood mononuclear cells (PBMC) of five patients with RA by enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (PCR). Tumor necrosis factor (TNF) was analyzed using PMA- activated THP-1 cells by ELISA. Suppression assay was analyzed using Treg cells and Teff cells isolated from RA patients by flow cytometry. Results In the CIA model, CKD-L and Tubastatin A significantly decreased the arthritis score. CKD-L increased CTLA-4 expression in Foxp3+ T cells and inhibited the proliferation of Teff cells in the suppression assay. In RA PBMC, CKD-L significantly inhibited TNF and interleukin (IL)-1β, and increased IL-10. CKD-L and Tubastatin A inhibited TNF secretion from PMA-activated THP-1 cells. CKD-L and ITF 2357 inhibited the proliferation of Teff cells in RA patients in the suppression assay. Tubastatin A had no effect on inhibition of proliferation. Conclusion CKD-L decreased the arthritis score in CIA, reduced the expression of TNF and IL-1β, and increased the expression of IL-10 in PBMC from RA patients. CKD-L increased CTLA-4 expression and the suppressive function of Treg cells. These results suggest that CKD-L may have a beneficial effect in the treatment of RA. | - |
dc.title | Therapeutic effect of a novel histone deacetylase 6 inhibitor, CKD-L, on collagen-induced arthritis in vivo and regulatory T cells in rheumatoid arthritis in vitro | - |
dc.type | Article | - |
dc.contributor.AlternativeAuthor | 오보람 | - |
dc.contributor.AlternativeAuthor | 서동현 | - |
dc.contributor.AlternativeAuthor | 배대권 | - |
dc.contributor.AlternativeAuthor | 하니나 | - |
dc.contributor.AlternativeAuthor | 최영일 | - |
dc.contributor.AlternativeAuthor | 주현정 | - |
dc.contributor.AlternativeAuthor | 박진경 | - |
dc.contributor.AlternativeAuthor | 이은영 | - |
dc.contributor.AlternativeAuthor | 이은봉 | - |
dc.contributor.AlternativeAuthor | 송영욱 | - |
dc.language.rfc3066 | en | - |
dc.rights.holder | The Author(s). | - |
dc.date.updated | 2017-07-09T03:23:53Z | - |
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