ArticleArthritis research & therapy2004
Increased AP-1 and NF-kappaB activation and recruitment with the combination of the proinflammatory cytokines IL-1beta, tumor necrosis factor alpha and IL-17 in rheumatoid synoviocytes.
Article in Arthritis research & therapy, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 80 citations in OpenAlex.
- Myeloid Activator Protein-1 Complex Contributes to Salt-Sensitive Hypertension.Circulation research · 2026Article
- Bioactive compounds from marine algae targeting MMP-9: A computational approach to rheumatoid arthritis treatment.Medicine · 2026Article
- The inhibitory effects ofFood science and biotechnology · 2026Article
- Review
- The Role of Synovitis and Latent Transcription Factors in the Pathogenesis of Rheumatoid Arthritis.Current rheumatology reviews · 2026Review
- Identification of a regulatory pathway governing TRAF1 via an arthritis-associated non-coding variant.Cell genomics · 2023Article
- Morphological and Mechanical Characterization of Extracellular Vesicles and Parent Human Synoviocytes under Physiological and Inflammatory Conditions.International journal of molecular sciences · 2022Article
- Local and systemic effects of IL-17 in joint inflammation: a historical perspective from discovery to targeting.Cellular & molecular immunology · 2021Review
- Th17 Cells in Periodontitis and Its Regulation by A20.Frontiers in immunology · 2021Review
- [Proinflammatory cytokines and cardio-vascular risk: From myocardial infarction tocytokine storm of COVID-19].Bulletin de l'Academie nationale de medecine · 2021Review
- The emerging role of fibroblast-like synoviocytes-mediated synovitis in osteoarthritis: An update.Journal of cellular and molecular medicine · 2020Review
- A cytokine protein-protein interaction network for identifying key molecules in rheumatoid arthritis.PloS one · 2018Article
- Transcriptional profiles of JIA patient blood with subsequent poor response to methotrexate.Rheumatology (Oxford, England) · 2017Article
- Inflammasomes in Inflammation-Induced Cancer.Frontiers in immunology · 2017Review
- IL-1β is a key cytokine that induces trypsin upregulation in the influenza virus-cytokine-trypsin cycle.Archives of virology · 2017Article
- LL202 protects against dextran sulfate sodium-induced experimental colitis in mice by inhibiting MAPK/AP-1 signaling.Oncotarget · 2016Article
- Bufalin, a bioactive component of the Chinese medicine chansu, inhibits inflammation and invasion of human rheumatoid arthritis fibroblast-like synoviocytes.Inflammation · 2014Article
- ANKRD1 acts as a transcriptional repressor of MMP13 via the AP-1 site.Molecular and cellular biology · 2014Article
- Enhanced inflammatory responses to toll-like receptor 2/4 stimulation in type 1 diabetic coronary artery endothelial cells: the effect of insulin.Cardiovascular diabetology · 2010Article
- Influenza virus-cytokine-protease cycle in the pathogenesis of vascular hyperpermeability in severe influenza.The Journal of infectious diseases · 2010Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
To determine the contribution of IL-1beta, tumor necrosis factor alpha (TNF-alpha) and IL-17 to AP-1, NF-kappaB and Egr-1 activation in rheumatoid arthritis, the effect of the cytokines used alone or in combination was measured on TF expression in rheumatoid synoviocytes. Effects on mRNA expression were measured by RT-PCR and effects on nuclear translocation were measured by immunocytochemistry. To assess the functional consequences of cytokine induction, osteoprotegerin levels were measured in synoviocyte supernatants.IL-1beta and TNF-alpha alone at optimal concentration (100 pg/ml) induced the nuclear translocation of NF-kappaB and almost all AP-1 members, except JunB and Egr-1 for IL-1beta and except Fra-2 and Egr-1 for TNF-alpha. IL-17 was clearly less potent since no nuclear translocation was observed, except for a weak activation of Fra-1 and NF-kappaB. More importantly, when these cytokines were used at low concentrations, their combination showed a synergistic effect on almost all the TFs, except for Egr-1, with a particular effect on Fra-1 and NF-kappaB. Increased recruitment of additional factors was induced when the three cytokines were combined. IL-1 and TNF-alpha induced mRNA expression of c-jun while IL-17 had no effect. A synergistic effect was seen with their combination. A similar synergistic effect was observed for osteoprotegerin production when these three cytokines were combined at low concentrations.AP-1 and NF-kappaB pathways were highly sensitive to the combination through synergistic mechanisms. These effects observed in rheumatoid arthritis synoviocytes may reflect the conditions found in the rheumatoid arthritis joint and may contribute to the mode of action of cytokine inhibitors.
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