PMID- 36047206
OWN - NLM
STAT- MEDLINE
DCOM- 20220908
LR  - 20220909
IS  - 1347-5215 (Electronic)
IS  - 0918-6158 (Linking)
VI  - 45
IP  - 9
DP  - 2022
TI  - A Novel HDAC1-Selective Inhibitor Attenuates Autoimmune Arthritis by Inhibiting 
      Inflammatory Cytokine Production.
PG  - 1364-1372
LID - 10.1248/bpb.b22-00321 [doi]
AB  - Rheumatoid arthritis (RA) is systemic autoimmune arthritis that causes joint 
      inflammation and destruction. Accumulating evidence has shown that inhibitors of 
      class I histone deacetylases (HDACs) (i.e., HDAC1, 2, 3, and 8) are potential 
      therapeutic candidates as targeted synthetic disease-modifying antirheumatic 
      drugs (tsDMARDs). Nevertheless, the inhibition of class I HDACs has severe 
      adverse effects because of their broad spectrum. We evaluated the therapeutic 
      effect of a novel selective HDAC1 inhibitor TTA03-107 for collagen-induced 
      arthritis (CIA) and collagen antibody-induced arthritis (CAIA) models in mice. We 
      also examined the effect of TTA03-107 in bone marrow-derived macrophages (BMDMs) 
      and T helper 17 (Th17) cells in vitro. Here, we delineate that TTA03-107 reduced 
      the severity of autoimmune arthritis without obvious adverse effects in CIA and 
      CAIA models. Moreover, TTA03-107 suppressed the production of inflammatory 
      cytokines, such as interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha, and 
      IL-17A, in serum and joint tissue. In vitro treatment of BMDMs with TTA03-107 
      dampened the M1 differentiation and inflammatory cytokine production. TTA03-107 
      also suppressed the differentiation of Th17 cells. These results demonstrate that 
      TTA03-107 can attenuate the development of arthritis in experimental RA models by 
      inhibiting the differentiation and activation of macrophages and Th17 cells. 
      Therefore, TTA03-107 is a potential tsDMARD candidate.
FAU - Zhe, Wei
AU  - Zhe W
AD  - Division of Biochemistry, Graduate School of Pharmaceutical Sciences and 
      Department of Pharmaceutical Sciences, Keio University Faculty of Pharmacy.
FAU - Hoshina, Naomi
AU  - Hoshina N
AD  - Division of Biochemistry, Graduate School of Pharmaceutical Sciences and 
      Department of Pharmaceutical Sciences, Keio University Faculty of Pharmacy.
FAU - Itoh, Yukihiro
AU  - Itoh Y
AD  - SANKEN, Osaka University.
FAU - Tojo, Toshifumi
AU  - Tojo T
AD  - Graduate School of Medical Science, Kyoto Prefectural University of Medicine.
FAU - Suzuki, Takayoshi
AU  - Suzuki T
AD  - SANKEN, Osaka University.
AD  - Graduate School of Medical Science, Kyoto Prefectural University of Medicine.
FAU - Hase, Koji
AU  - Hase K
AD  - Division of Biochemistry, Graduate School of Pharmaceutical Sciences and 
      Department of Pharmaceutical Sciences, Keio University Faculty of Pharmacy.
AD  - The Institute of Fermentation Sciences (IFeS), Faculty of Food and Agricultural 
      Sciences, Fukushima University.
FAU - Takahashi, Daisuke
AU  - Takahashi D
AD  - Division of Biochemistry, Graduate School of Pharmaceutical Sciences and 
      Department of Pharmaceutical Sciences, Keio University Faculty of Pharmacy.
LA  - eng
PT  - Journal Article
PL  - Japan
TA  - Biol Pharm Bull
JT  - Biological & pharmaceutical bulletin
JID - 9311984
RN  - 0 (Antirheumatic Agents)
RN  - 0 (Cytokines)
RN  - 0 (Histone Deacetylase Inhibitors)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Animals
MH  - *Antirheumatic Agents/therapeutic use
MH  - *Arthritis, Experimental/pathology
MH  - *Arthritis, Rheumatoid/drug therapy/pathology
MH  - Cytokines/metabolism
MH  - *Histone Deacetylase Inhibitors/therapeutic use
MH  - Mice
MH  - Th17 Cells
MH  - Tumor Necrosis Factor-alpha/metabolism
OTO - NOTNLM
OT  - T helper 17 cell
OT  - collagen antibody-induced arthritis
OT  - collagen-induced arthritis
OT  - histone deacetylase 1 inhibitor
OT  - macrophage
OT  - rheumatoid arthritis
EDAT- 2022/09/02 06:00
MHDA- 2022/09/09 06:00
CRDT- 2022/09/01 03:46
PHST- 2022/09/01 03:46 [entrez]
PHST- 2022/09/02 06:00 [pubmed]
PHST- 2022/09/09 06:00 [medline]
AID - 10.1248/bpb.b22-00321 [doi]
PST - ppublish
SO  - Biol Pharm Bull. 2022;45(9):1364-1372. doi: 10.1248/bpb.b22-00321.