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.
Collagen
Janus kinase/signal transducers and activators of the transcription
fibroblast cell culture
tofacitinib
Journal
Archives of rheumatology
ISSN: 2618-6500
Titre abrégé: Arch Rheumatol
Pays: Turkey
ID NLM: 101639000
Informations de publication
Date de publication:
Sep 2020
Sep 2020
Historique:
received:
30
04
2019
accepted:
24
09
2019
entrez:
18
1
2021
pubmed:
19
1
2021
medline:
19
1
2021
Statut:
epublish
Résumé
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. BJ-CRL-1474® (skin) and BRL3A® (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-β1), and hydroxyproline levels were measured using the enzyme-linked immunosorbent assay method. 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-β1 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). 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.
Identifiants
pubmed: 33458657
doi: 10.46497/ArchRheumatol.2020.7568
pmc: PMC7788643
doi:
Types de publication
Journal Article
Langues
eng
Pagination
343-350Informations de copyright
Copyright © 2020, Turkish League Against Rheumatism.
Déclaration de conflit d'intérêts
Conflict of Interest: The authors declared no conflicts of interest with respect to the authorship and/or publication of this article.
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