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
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 o...
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| Format: | Article |
| Language: | English |
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BMC
2017-07-01
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| Series: | Arthritis Research & Therapy |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13075-017-1357-2 |
| _version_ | 1819079460649959424 |
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| author | Bo Ram Oh Dong-hyeon Suh Daekwon Bae Nina Ha Young Il Choi Hyun Jung Yoo Jin Kyun Park Eun Young Lee Eun Bong Lee Yeong Wook Song |
| author_facet | Bo Ram Oh Dong-hyeon Suh Daekwon Bae Nina Ha Young Il Choi Hyun Jung Yoo Jin Kyun Park Eun Young Lee Eun Bong Lee Yeong Wook Song |
| author_sort | Bo Ram Oh |
| collection | DOAJ |
| 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/1 J mice. Mice were treated with HDAC inhibitor for 18 days. 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. |
| first_indexed | 2024-12-21T19:29:21Z |
| format | Article |
| id | doaj.art-032a1b1e16d54ae78ab025989e29ca41 |
| institution | Directory Open Access Journal |
| issn | 1478-6362 |
| language | English |
| last_indexed | 2024-12-21T19:29:21Z |
| publishDate | 2017-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Arthritis Research & Therapy |
| spelling | doaj.art-032a1b1e16d54ae78ab025989e29ca412022-12-21T18:52:44ZengBMCArthritis Research & Therapy1478-63622017-07-0119111610.1186/s13075-017-1357-2Therapeutic effect of a novel histone deacetylase 6 inhibitor, CKD-L, on collagen-induced arthritis in vivo and regulatory T cells in rheumatoid arthritis in vitroBo Ram Oh0Dong-hyeon Suh1Daekwon Bae2Nina Ha3Young Il Choi4Hyun Jung Yoo5Jin Kyun Park6Eun Young Lee7Eun Bong Lee8Yeong Wook Song9Department of Molecular Medicine and Biopharmaceutical Sciences, BK 21 plus Graduate School of Convergence Science and Technology, College of Medicine, Seoul National UniversityDepartment of Pharmacology and Toxicology, CKD Research Institute, CKD Pharmaceutical CompanyDepartment of Pharmacology and Toxicology, CKD Research Institute, CKD Pharmaceutical CompanyDepartment of Pharmacology and Toxicology, CKD Research Institute, CKD Pharmaceutical CompanyDepartment of Pharmacology and Toxicology, CKD Research Institute, CKD Pharmaceutical CompanyDivision of Rheumatology, Department of Internal Medicine, Seoul National University College of MedicineDivision of Rheumatology, Department of Internal Medicine, Seoul National University College of MedicineDivision of Rheumatology, Department of Internal Medicine, Seoul National University College of MedicineDivision of Rheumatology, Department of Internal Medicine, Seoul National University College of MedicineDepartment of Molecular Medicine and Biopharmaceutical Sciences, BK 21 plus Graduate School of Convergence Science and Technology, College of Medicine, Seoul National UniversityAbstract 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/1 J mice. Mice were treated with HDAC inhibitor for 18 days. 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.http://link.springer.com/article/10.1186/s13075-017-1357-2Histone deacetylase 6Histone deacetylase inhibitorRheumatoid arthritisCollagen-induced arthritisRegulatory T cell |
| spellingShingle | Bo Ram Oh Dong-hyeon Suh Daekwon Bae Nina Ha Young Il Choi Hyun Jung Yoo Jin Kyun Park Eun Young Lee Eun Bong Lee Yeong Wook Song 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 Arthritis Research & Therapy Histone deacetylase 6 Histone deacetylase inhibitor Rheumatoid arthritis Collagen-induced arthritis Regulatory T cell |
| 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | Histone deacetylase 6 Histone deacetylase inhibitor Rheumatoid arthritis Collagen-induced arthritis Regulatory T cell |
| url | http://link.springer.com/article/10.1186/s13075-017-1357-2 |
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