ArticleArthritis research & therapy2016
p53 predominantly regulates IL-6 production and suppresses synovial inflammation in fibroblast-like synoviocytes and adjuvant-induced arthritis.
Article in Arthritis research & therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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41 citing papers in PubMed, 65 citations in OpenAlex.
- TAK1 inhibition restores p53 expression and suppresses inflammation and hyperplasia in JIA synovial fibroblasts.Rheumatology (Oxford, England) · 2026Article
- Pharmacological intervention of Chinese medicine via regulating ferroptosis in gastric cancer.Chinese medicine · 2026Review
- Insights from pharmacovigilance databases, clinical cohorts and preclinical models into VEGF(R) inhibitor-induced arthritis in cancer.Communications medicine · 2025Article
- Dysregulation of Different Modes of Programmed Cell Death in Rheumatoid Arthritis Fibroblast-Like Synoviocyte.International journal of rheumatic diseases · 2025Review
- Regulation of Autophagy by the Cdk1/p53/p21 Feedback Loop in an Interstitial Cystitis/Bladder Pain Syndrome Cell Model: Implications for Inflammatory Response.International urogynecology journal · 2025Article
- P53 Regulation upon Lipid Peroxidation and Ferroptosis for Intervention against Atherogenesis.Current medicinal chemistry · 2025Review
- Pharmacogenomics of TNF inhibitors.Frontiers in immunology · 2025Review
- Article
- Identification of diagnostic signature, molecular subtypes, and potential drugs in allergic rhinitis based on an inflammatory response gene set.Frontiers in immunology · 2024Article
- Resveratrol promotes apoptosis and G2/M cell cycle arrest of fibroblast-like synoviocytes in rheumatoid arthritis through regulation of autophagy and the serine-threonine kinase-p53 axis.Archives of medical science : AMS · 2024Article
- Aquaporin 1 is renoprotective in septic acute kidney injury by attenuating inflammation, apoptosis and fibrosis through inhibition of P53 expression.Frontiers in immunology · 2024Article
- Mutant p53Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023Article
- Treatment with FAP-targeted zinc ferrite nanoparticles for rheumatoid arthritis by inducing endoplasmic reticulum stress and mitochondrial damage.Materials today. Bio · 2023Article
- Activated CD90/Thy-1 fibroblasts co-express the Δ133p53β isoform and are associated with highly inflamed rheumatoid arthritis.Arthritis research & therapy · 2023Article
- Role of reactive oxygen species and mitochondrial damage in rheumatoid arthritis and targeted drugs.Frontiers in immunology · 2023Review
- Blocking TRPV4 Ameliorates Osteoarthritis by Inhibiting M1 Macrophage Polarization via the ROS/NLRP3 Signaling Pathway.Antioxidants (Basel, Switzerland) · 2022Article
- Bacterial Compositional Shifts of Gut Microbiomes in Patients with Rheumatoid Arthritis in Association with Disease Activity.Microorganisms · 2022Article
- Inflammation suppresses DLG2 expression decreasing inflammasome formation.Journal of cancer research and clinical oncology · 2022Article
- Integrating network pharmacology and experimental validation to clarify the anti-hyperuricemia mechanism of cortex phellodendri in mice.Frontiers in pharmacology · 2022Article
- Modulation of anti-angiogenic activity using ultrasound-activated nutlin-loaded piezoelectric nanovectors.Materials today. Bio · 2022Article
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDominant-negative somatic mutations of p53 has been identified in the synovium of patients with rheumatoid arthritis (RA), in which interleukin (IL)-6 has been established as a pivotal inflammatory cytokine. The aim of this study was to clarify the significance of p53 in the longstanding inflammation in RA by modulating IL-6.
methodsWe established adjuvant-induced arthritis (AIA) in Lewis rats and treated them with p53 activator, and then analyzed the histopathology of the synovium and IL-6 expression. Human fibroblast-like synoviocytes (FLS) were cultured and transfected with p53-siRNA or transduced with adenovirus (Ad)-p53, and then assessed with MTT, TUNEL staining, and luciferase assay. IL-1β, tumor necrosis factor (TNF)-α and IL-17 were used to stimulate FLS, and subsequent IL-6 expression as well as relevant signal pathways were explored.
resultsp53 significantly reduced synovitis as well as the IL-6 level in the AIA rats. It controlled cell cycle arrest and proliferation, but not apoptosis. Proinflammatory cytokines inhibited p53 expression in FLS, while p53 significantly suppressed the production of IL-6. Furthermore, IL-6 expression in p53-deficient FLS was profoundly reduced by NF-kappaB, p38, JNK, and ERK inhibitors.
conclusionOur findings reveal a novel function of p53 in controlling inflammatory responses and suggest that p53 abnormalities in RA could sustain and accelerate synovial inflammation mainly through IL-6. p53 may be a key modulator of IL-6 in the synovium and plays a pivotal role in suppressing inflammation by interaction with the signal pathways in RA-FLS. Interfering with the p53 pathway could therefore be an effective strategy to treat RA.
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