PMID- 33458657
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220420
IS  - 2618-6500 (Electronic)
IS  - 2148-5046 (Print)
IS  - 2148-5046 (Linking)
VI  - 35
IP  - 3
DP  - 2020 Sep
TI  - The Effects of Tofacitinib-Mediated Janus Kinase/Signal Transducers and 
      Activators of the Transcription Signal Pathway Inhibition on Collagen 
      Biosynthesis in Hepatic and Skin Fibroblast Cell Culture.
PG  - 343-350
LID - 10.46497/ArchRheumatol.2020.7568 [doi]
AB  - OBJECTIVES: This study aims to investigate the effects of Janus kinase/signal 
      transducers and activators of the transcription (JAK/STAT) pathway inhibition on 
      collagen biosynthesis in fibroblast cell culture by tofacitinib. MATERIALS AND 
      METHODS: BJ-CRL-1474(R) (skin) and BRL3A(R) (hepatic) fibroblast cell cultures were 
      proliferated in a suitable medium. Tofacitinib was administered to fibroblast 
      cells proliferating in 96-well flasks at concentrations of 25, 50, 100, 200, 400, 
      and 800 nM. Tissue inhibitor of metalloproteinase-1 (TIMP-1), matrix 
      metalloproteinase-3 (MMP-3), transforming growth factor beta 1 (TGF-beta1), and 
      hydroxyproline levels were measured using the enzyme-linked immunosorbent assay 
      method. RESULTS: Tofacitinib showed cytotoxic effect on skin and liver cell 
      culture. The cytotoxic effect of tofacitinib started at 100 nM (p<0.05). The 
      highest effect was obtained at 800 nM. The time-dependent cytotoxic effect of 
      tofacitinib was significantly higher at all concentrations after 72 hours than at 
      24 and 48 hours (p<0.05). The level of TGF-beta1 was significantly lower even at a 
      tofacitinib concentration of 25 nM (p<0.05). There were significant decreases in 
      MMP-3, TIMP-1, and hydroxyproline levels after tofacitinib administration 
      (p<0.05). CONCLUSION: Tofacitinib inhibited fibroblast cell proliferation in a 
      concentration-dependent manner in a fibroblast cell culture. However, further 
      extensive animal and human studies are necessary to determine the clinical 
      significance of this effect.
CI  - Copyright (c) 2020, Turkish League Against Rheumatism.
FAU - SahIn, Mehtap
AU  - SahIn M
AUID- ORCID: 0000-0003-4518-6489
AD  - Department of Medical Biochemistry, Sivas Cumhuriyet University Medical Faculty, 
      Sivas, Turkey.
FAU - Aydin, Huseyin
AU  - Aydin H
AUID- ORCID: 0000-0002-3194-830X
AD  - Department of Medical Biochemistry, Sivas Cumhuriyet University Medical Faculty, 
      Sivas, Turkey.
FAU - Altun, Ahmet
AU  - Altun A
AUID- ORCID: 0000-0003-2056-8683
AD  - Department of Pharmacology, Sivas Cumhuriyet University Medical Faculty, Sivas, 
      Turkey.
FAU - DerIn, Mehmet Emin
AU  - DerIn ME
AUID- ORCID: 0000-0002-8830-8848
AD  - Department of Internal Medicine, Rheumatology Unit, Sivas Cumhuriyet University 
      Medical Faculty, Sivas, Turkey.
FAU - SahIn, Ali
AU  - SahIn A
AUID- ORCID: 0000-0002-6953-4276
AD  - Department of Internal Medicine, Rheumatology Unit, Sivas Cumhuriyet University 
      Medical Faculty, Sivas, Turkey.
LA  - eng
PT  - Journal Article
DEP - 20200207
PL  - Turkey
TA  - Arch Rheumatol
JT  - Archives of rheumatology
JID - 101639000
PMC - PMC7788643
OTO - NOTNLM
OT  - Collagen
OT  - Janus kinase/signal transducers and activators of the transcription
OT  - fibroblast cell culture
OT  - tofacitinib
COIS- Conflict of Interest: The authors declared no conflicts of interest with respect 
      to the authorship and/or publication of this article.
EDAT- 2021/01/19 06:00
MHDA- 2021/01/19 06:01
PMCR- 2020/02/07
CRDT- 2021/01/18 05:36
PHST- 2019/04/30 00:00 [received]
PHST- 2019/09/24 00:00 [accepted]
PHST- 2021/01/18 05:36 [entrez]
PHST- 2021/01/19 06:00 [pubmed]
PHST- 2021/01/19 06:01 [medline]
PHST- 2020/02/07 00:00 [pmc-release]
AID - 10.46497/ArchRheumatol.2020.7568 [doi]
PST - epublish
SO  - Arch Rheumatol. 2020 Feb 7;35(3):343-350. doi: 10.46497/ArchRheumatol.2020.7568. 
      eCollection 2020 Sep.