PMID- 36253500
OWN - NLM
STAT- MEDLINE
DCOM- 20230321
LR  - 20230321
IS  - 1573-2576 (Electronic)
IS  - 0360-3997 (Linking)
VI  - 46
IP  - 2
DP  - 2023 Apr
TI  - Dimethyl Fumarate Inhibits Fibroblast Like Synoviocytes-mediated Inflammation and 
      Joint Destruction in Rheumatoid Arthritis.
PG  - 612-622
LID - 10.1007/s10753-022-01759-1 [doi]
AB  - Rheumatoid arthritis (RA) as a chronic inflammatory disorder affects around 1% of 
      the world population. Fibroblast-like synoviocyte (FLS), one of the main cells in 
      RA pathogenesis is characterized by hyperproliferation and resistance to 
      apoptosis resulting to synovial hyperplasia. Dimethyl fumarate (DMF) has been 
      licensed for the treatment of multiple sclerosis (MS) and psoriasis; however, its 
      role in RA is unknown. DMF has immunomodulatory properties and may be considered 
      as therapeutic approach in RA treatment. In this study, we aimed to investigate 
      the effect of DMF on controlling FLS-mediated synovial inflammation and joint 
      destruction in RA. FLSs were isolated from synovial tissues of 8 patients with RA 
      and treated with DMF. Apoptosis rate was analyzed by Annexin V-FITC. Cell 
      proliferation was measured by carboxyfluorescein succinimidyl ester (CFSE) dye. 
      The matrix metalloproteinase 3 (MMP3) and NF-small ka, CyrillicB pathway protein (p65) mRNA 
      expression were evaluated by RT-PCR. Also, the IL-6 production and lactate 
      release were measured in FLS supernatant. DMF treatment decreased the cell 
      proliferation and increased apoptosis in a dose dependent manner. DMF-treated FLS 
      showed a reduction in IL-6 and lactate release. Moreover, it was revealed that 
      DMF inhibited the expression of p65 and MMP3. Our data demonstrate that DMF 
      treatment suppresses the aggressive and inflammatory features of RA FLSs. Our 
      Results suggest that DMF might be expected to be evaluated as a therapy for RA.
CI  - (c) 2022. The Author(s), under exclusive licence to Springer Science+Business 
      Media, LLC, part of Springer Nature.
FAU - Zafari, Parisa
AU  - Zafari P
AD  - Department of Immunology, Faculty of Medicine, Mazandaran University of Medical 
      Sciences, Sari, Iran.
FAU - Taghadosi, Mahdi
AU  - Taghadosi M
AD  - Department of Immunology, Faculty of Medicine, Kermanshah University of Medical 
      Sciences, Kermanshah, Iran.
FAU - Faramarzi, Fatemeh
AU  - Faramarzi F
AD  - Department of Immunology, Faculty of Medicine, Mazandaran University of Medical 
      Sciences, Sari, Iran.
FAU - Rajabinejad, Misagh
AU  - Rajabinejad M
AD  - Department of Immunology, Faculty of Medicine, Mazandaran University of Medical 
      Sciences, Sari, Iran.
FAU - Rafiei, Alireza
AU  - Rafiei A
AUID- ORCID: 0000-0002-1766-6605
AD  - Department of Immunology, Faculty of Medicine, Mazandaran University of Medical 
      Sciences, Sari, Iran. rafiei1710@gmail.com.
LA  - eng
GR  - 3123/Mazandaran University of Medical Sciences/
PT  - Journal Article
DEP - 20221017
PL  - United States
TA  - Inflammation
JT  - Inflammation
JID - 7600105
RN  - FO2303MNI2 (Dimethyl Fumarate)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
RN  - 0 (Interleukin-6)
SB  - IM
MH  - Humans
MH  - *Synoviocytes/metabolism
MH  - Dimethyl Fumarate/pharmacology/therapeutic use
MH  - Matrix Metalloproteinase 3
MH  - Interleukin-6/metabolism
MH  - *Arthritis, Rheumatoid/metabolism
MH  - Synovial Membrane/metabolism
MH  - Inflammation/metabolism
MH  - Fibroblasts/metabolism
MH  - Cell Proliferation
MH  - Cells, Cultured
OTO - NOTNLM
OT  - dimethyl fumarate.
OT  - fibroblast like synoviocyte
OT  - inflammation
OT  - rheumatoid arthritis
EDAT- 2022/10/18 06:00
MHDA- 2023/03/22 06:00
CRDT- 2022/10/17 23:29
PHST- 2022/08/03 00:00 [received]
PHST- 2022/10/12 00:00 [accepted]
PHST- 2022/09/06 00:00 [revised]
PHST- 2022/10/18 06:00 [pubmed]
PHST- 2023/03/22 06:00 [medline]
PHST- 2022/10/17 23:29 [entrez]
AID - 10.1007/s10753-022-01759-1 [pii]
AID - 10.1007/s10753-022-01759-1 [doi]
PST - ppublish
SO  - Inflammation. 2023 Apr;46(2):612-622. doi: 10.1007/s10753-022-01759-1. Epub 2022 
      Oct 17.