In vitro pharmacological effects of peficitinib on lymphocyte activation: a potential treatment for systemic sclerosis with JAK inhibitors.
Adamantane
/ analogs & derivatives
Arthritis, Rheumatoid
/ metabolism
Female
Humans
Janus Kinase Inhibitors
/ pharmacology
Lymphocyte Activation
/ drug effects
Lymphocytes
/ drug effects
Male
Niacinamide
/ analogs & derivatives
Phosphorylation
/ drug effects
STAT Transcription Factors
/ metabolism
Scleroderma, Systemic
/ metabolism
Janus kinase
RA
SSc
peficitinib
signal transducer and activator of transcription
Journal
Rheumatology (Oxford, England)
ISSN: 1462-0332
Titre abrégé: Rheumatology (Oxford)
Pays: England
ID NLM: 100883501
Informations de publication
Date de publication:
01 08 2020
01 08 2020
Historique:
received:
08
07
2019
revised:
06
10
2019
pubmed:
26
11
2019
medline:
20
1
2021
entrez:
26
11
2019
Statut:
ppublish
Résumé
Peficitinib, a novel Janus kinase (JAK) inhibitor, demonstrated promising results in treating RA in phase 3 clinical trials. This in vitro study was undertaken to characterize the pharmacological properties of peficitinib and investigate the involvement of JAK and signal transducer and activator of transcription (STAT) pathways in the pathological processes of SSc, which is also an autoimmune disease. Phosphorylation levels of STAT molecules were assessed in peripheral blood mononuclear cells collected from patients with RA or SSc and healthy subjects, and in skin specimens obtained from 19 patients with SSc. In vitro inhibition of STAT phosphorylation and cytokine/chemokine production by peficitinib, tofacitinib and baricitinib were also characterized. Higher spontaneous STAT1 or STAT3 phosphorylation was observed in peripheral T-cells and monocytes from patients with RA and SSc compared with healthy subjects. In skin sections from patients with SSc, phosphorylated STAT3-positive cells were found in almost all cases, irrespective of disease subtype or patient characteristics. Conversely, phosphorylated STAT1-positive cells were observed only in samples from untreated patients with diffuse disease of short duration. Peficitinib inhibited STAT phosphorylation induced by various cytokines, with comparable efficacy to tofacitinib and baricitinib. Peficitinib also suppressed cytokine and chemokine production by peripheral blood mononuclear cells and skin fibroblasts. Our results suggest that JAK/STAT pathways are constitutively activated in SSc and RA, and that the JAK inhibitor may represent a novel therapeutic option for SSc.
Identifiants
pubmed: 31764973
pii: 5640529
doi: 10.1093/rheumatology/kez526
pmc: PMC7382595
doi:
Substances chimiques
Janus Kinase Inhibitors
0
STAT Transcription Factors
0
Niacinamide
25X51I8RD4
peficitinib
HPH1166CKX
Adamantane
PJY633525U
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1957-1968Informations de copyright
© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology.
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