PMID- 28673326
OWN - NLM
STAT- MEDLINE
DCOM- 20180403
LR  - 20181113
IS  - 1478-6362 (Electronic)
IS  - 1478-6354 (Linking)
VI  - 19
IP  - 1
DP  - 2017 Jul 3
TI  - 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.
PG  - 154
LID - 10.1186/s13075-017-1357-2 [doi]
AB  - 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)-1beta, 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-1beta, 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.
FAU - Oh, Bo Ram
AU  - Oh BR
AD  - Department of Molecular Medicine and Biopharmaceutical Sciences, BK 21 plus
      Graduate School of Convergence Science and Technology, College of Medicine, Seoul
      National University, Seoul, Korea.
FAU - Suh, Dong-Hyeon
AU  - Suh DH
AD  - Department of Pharmacology and Toxicology, CKD Research Institute, CKD
      Pharmaceutical Company, Seoul, Korea.
FAU - Bae, Daekwon
AU  - Bae D
AD  - Department of Pharmacology and Toxicology, CKD Research Institute, CKD
      Pharmaceutical Company, Seoul, Korea.
FAU - Ha, Nina
AU  - Ha N
AD  - Department of Pharmacology and Toxicology, CKD Research Institute, CKD
      Pharmaceutical Company, Seoul, Korea.
FAU - Choi, Young Il
AU  - Choi YI
AD  - Department of Pharmacology and Toxicology, CKD Research Institute, CKD
      Pharmaceutical Company, Seoul, Korea.
FAU - Yoo, Hyun Jung
AU  - Yoo HJ
AD  - Division of Rheumatology, Department of Internal Medicine, Seoul National
      University College of Medicine, Seoul, Korea.
FAU - Park, Jin Kyun
AU  - Park JK
AD  - Division of Rheumatology, Department of Internal Medicine, Seoul National
      University College of Medicine, Seoul, Korea.
FAU - Lee, Eun Young
AU  - Lee EY
AD  - Division of Rheumatology, Department of Internal Medicine, Seoul National
      University College of Medicine, Seoul, Korea.
FAU - Lee, Eun Bong
AU  - Lee EB
AD  - Division of Rheumatology, Department of Internal Medicine, Seoul National
      University College of Medicine, Seoul, Korea.
FAU - Song, Yeong Wook
AU  - Song YW
AD  - Department of Molecular Medicine and Biopharmaceutical Sciences, BK 21 plus
      Graduate School of Convergence Science and Technology, College of Medicine, Seoul
      National University, Seoul, Korea. ysong@snu.ac.kr.
AD  - Division of Rheumatology, Department of Internal Medicine, Seoul National
      University College of Medicine, Seoul, Korea. ysong@snu.ac.kr.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170703
PL  - England
TA  - Arthritis Res Ther
JT  - Arthritis research & therapy
JID - 101154438
RN  - 0 (Histone Deacetylase Inhibitors)
RN  - EC 3.5.1.98 (Hdac6 protein, mouse)
RN  - EC 3.5.1.98 (Histone Deacetylase 6)
SB  - IM
MH  - Animals
MH  - Arthritis, Experimental/*drug therapy/immunology/metabolism
MH  - Cell Survival/drug effects/physiology
MH  - Cells, Cultured
MH  - Dose-Response Relationship, Drug
MH  - Histone Deacetylase 6/*antagonists & inhibitors/metabolism
MH  - Histone Deacetylase Inhibitors/pharmacology/*therapeutic use
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Inbred DBA
MH  - T-Lymphocytes, Regulatory/*drug effects/immunology/metabolism
MH  - Treatment Outcome
PMC - PMC5496370
OTO - NOTNLM
OT  - *Collagen-induced arthritis
OT  - *Histone deacetylase 6
OT  - *Histone deacetylase inhibitor
OT  - *Regulatory T cell
OT  - *Rheumatoid arthritis
EDAT- 2017/07/05 06:00
MHDA- 2018/04/04 06:00
CRDT- 2017/07/05 06:00
PHST- 2017/02/27 00:00 [received]
PHST- 2017/06/01 00:00 [accepted]
PHST- 2017/07/05 06:00 [entrez]
PHST- 2017/07/05 06:00 [pubmed]
PHST- 2018/04/04 06:00 [medline]
AID - 10.1186/s13075-017-1357-2 [doi]
AID - 10.1186/s13075-017-1357-2 [pii]
PST - epublish
SO  - Arthritis Res Ther. 2017 Jul 3;19(1):154. doi: 10.1186/s13075-017-1357-2.