ArticleClinical and experimental immunology2013
Inhibition of Janus kinase/signal transducer and activator of transcription (JAK/STAT) signalling pathway in rheumatoid synovial fibroblasts using small molecule compounds.
Article in Clinical and experimental immunology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04789850 (Safety and Efficacy of Itacitinib in Adults With Systemic Sclerosis), which is not on this map. Cited by 22 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Safety and Efficacy of Itacitinib in Adults With Systemic Sclerosis: a Phase II, Randomized, Controlled Trial
Who cites it
22 citing papers in PubMed, 42 citations in OpenAlex.
- Tofacitinib blocks IFN-regulated biomarker genes in skin fibroblasts and keratinocytes in a systemic sclerosis trial.JCI insight · 2022Trial
- Review
- Estragole Ameliorates CFA Induced Rheumatoid Arthritis Symptoms in Wistar Rats by Inhibiting JAK-2/STAT-3 Pathway.Physiological research · 2024Article
- Antibodies of the immunoglobulin a isotype to novel antigens in early axial spondyloarthritis.Frontiers in medicine · 2022Article
- Aconiti lateralis radix praeparata total alkaloids exert anti-RA effects by regulating NF-κB and JAK/STAT signaling pathways and promoting apoptosis.Frontiers in pharmacology · 2022Article
- Targeting of Janus Kinases Limits Pro-Inflammatory but Also Immunosuppressive Circuits in the Crosstalk between Synovial Fibroblasts and Lymphocytes.Biomedicines · 2021Article
- JAK1: Number one in the family; number one in inflammation?Rheumatology (Oxford, England) · 2021Article
- Drug repurposing and cytokine management in response to COVID-19: A review.International immunopharmacology · 2020Review
- tRNA-derived fragments (tRFs) regulate post-transcriptional gene expression via AGO-dependent mechanism in IL-1β stimulated chondrocytes.Osteoarthritis and cartilage · 2020Article
- Hi-Frontiers in medicine · 2020Review
- CCDC7 Activates Interleukin-6 and Vascular Endothelial Growth Factor to Promote Proliferation via the JAK-STAT3 Pathway in Cervical Cancer Cells.OncoTargets and therapy · 2020Article
- Deriving a Boolean dynamics to reveal macrophage activation with in vitro temporal cytokine expression profiles.BMC bioinformatics · 2019Article
- Current Therapeutic Options in the Treatment of Rheumatoid Arthritis.Journal of clinical medicine · 2019Review
- Curculigoside exerts significant anti‑arthritic effects in vivo and in vitro via regulation of the JAK/STAT/NF‑κB signaling pathway.Molecular medicine reports · 2019Article
- Clinical efficacy of launched JAK inhibitors in rheumatoid arthritis.Rheumatology (Oxford, England) · 2019Review
- Targeting Activated Synovial Fibroblasts in Rheumatoid Arthritis by Peficitinib.Frontiers in immunology · 2019Article
- The barrier hypothesis and Oncostatin M: Restoration of epithelial barrier function as a novel therapeutic strategy for the treatment of type 2 inflammatory disease.Tissue barriers · 2017Review
- Baseline JAK phosphorylation profile of peripheral blood leukocytes, studied by whole blood phosphospecific flow cytometry, is associated with 1-year treatment response in early rheumatoid arthritis.Arthritis research & therapy · 2017Article
- Oncostatin M promotes mucosal epithelial barrier dysfunction, and its expression is increased in patients with eosinophilic mucosal disease.The Journal of allergy and clinical immunology · 2015Article
- New treatments for inflammatory rheumatic disease.Immunologic research · 2014Review
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Janus kinase (JAK) inhibitors have been developed as anti-inflammatory agents and have demonstrated clinical efficacy in rheumatoid arthritis (RA). We investigated if JAK-3-selective inhibition alone could disrupt cytokine signalling in rheumatoid synovial fibroblasts. In-vitro studies were performed using synovial fibroblasts isolated from patients with RA. Levels of activated JAK and signal transducer and activator of transcription (STAT) proteins were detected by immunoblot analysis. Target-gene expression levels were measured by reverse transcription-polymerase chain reaction (RT-PCR) or real-time PCR. The JAK inhibitors CP-690,550 and INCB028050 both suppressed activation of JAK-1/-2/-3 and downstream STAT-1/-3/-5, as well as the expression levels of target proinflammatory genes (MCP-I, SAA1/2) in oncostatin-M (OSM)-stimulated rheumatoid synovial fibroblasts. In contrast, the JAK-3-selective inhibitor, PF-956980, suppressed STAT-1/-5 activation but did not affect STAT-3 activation in OSM-stimulated rheumatoid synovial fibroblasts. In addition, PF-956980 significantly suppressed MCP-1 gene expression, but did not block SAA1/2 gene expression in OSM-stimulated rheumatoid synovial fibroblasts. These data suggest that JAK-3-selective inhibition alone is insufficient to control STAT-3-dependent signalling in rheumatoid synovial fibroblasts, and inhibition of JAKs, including JAK-1/-2, is needed to control the proinflammatory cascade in RA.
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