ArticleRheumatology (Oxford, England)2015
Methotrexate-mediated inhibition of nuclear factor κB activation by distinct pathways in T cells and fibroblast-like synoviocytes.
Article in Rheumatology (Oxford, England), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 68 citations in OpenAlex.
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- Organoid drug profiling identifies methotrexate as a therapy for SCCOHT, a rare pediatric cancer.Science advances · 2025Article
- Dual-Responsive Methotrexate-Human Serum Albumin Complex-Encapsulated Liposomes for Targeted and Enhanced Atherosclerosis Therapy.International journal of nanomedicine · 2025Article
- Methotrexate promotes the release of granulocyte-macrophage colony-stimulating factor from rheumatoid arthritis fibroblast-like synoviocytes via autocrine interleukin-1 signaling.Arthritis research & therapy · 2024Article
- Microneedles loaded with cerium-manganese oxide nanoparticles for targeting macrophages in the treatment of rheumatoid arthritis.Journal of nanobiotechnology · 2024Article
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- A large-scale Boolean model of the rheumatoid arthritis fibroblast-like synoviocytes predicts drug synergies in the arthritic joint.NPJ systems biology and applications · 2023Article
- TAp63, a methotrexate target in CD4+ T cells, suppresses Foxp3 expression and exacerbates autoimmune arthritis.JCI insight · 2023Article
- The actions of methotrexate on endothelial cells are dependent on the shear stress-induced regulation of one carbon metabolism.Frontiers in immunology · 2023Article
- Methotrexate-loaded nanoparticles ameliorate experimental model of autoimmune arthritis by regulating the balance of interleukin-17-producing T cells and regulatory T cells.Journal of translational medicine · 2022Article
- Two Main Cellular Components in Rheumatoid Arthritis: Communication Between T Cells and Fibroblast-Like Synoviocytes in the Joint Synovium.Frontiers in immunology · 2022Review
- Methotrexate Alters the Expression of microRNA in Fibroblast-like Synovial Cells in Rheumatoid Arthritis.International journal of molecular sciences · 2021Article
- Dysregulation of lncRNAs in Rheumatoid Arthritis: Biomarkers, Pathogenesis and Potential Therapeutic Targets.Frontiers in pharmacology · 2021Review
- Article
- Modification of DNA structure by reactive nitrogen species as a result of 2-methoxyestradiol-induced neuronal nitric oxide synthase uncoupling in metastatic osteosarcoma cells.Redox biology · 2020Article
- Methotrexate and its mechanisms of action in inflammatory arthritis.Nature reviews. Rheumatology · 2020Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
objectivesNuclear factor κB (NF-κB) is a critical activator of inflammatory processes and MTX is one of the most commonly prescribed DMARDs for treatment of RA. We sought to determine whether MTX inhibited NF-κB activity in RA and in lymphocytes and fibroblast-like synoviocytes (FLSs) and to define underlying mechanisms of action.
methodsAn NF-κB luciferase reporter plasmid was used to measure NF-κB activation across experimental stimuli. Flow cytometry was used to quantify changes in intracellular protein levels, measure levels of reactive oxygen species and determine apoptosis. Quantitative RT-PCR was used to identify changes in MTX target genes.
resultsIn T cell lines, MTX (0.1 μM) inhibited activation of NF-κB via depletion of tetrahydrobiopterin (BH4) and increased Jun-N-terminal kinase (JNK)-dependent p53 activity. Inhibitors of BH4 activity or synthesis also inhibited NF-κB activation and, similar to MTX, increased JNK, p53, p21 and JUN activity. Patients with RA expressed increased levels of phosphorylated or active RelA (p65) compared with controls. Levels of phosphorylated RelA were reduced in patients receiving low-dose MTX therapy. In contrast, inhibition of NF-κB activation by MTX was not mediated via BH4 depletion and JNK activation in FLSs, but rather was completely prevented by adenosine receptor antagonists.
conclusionOur findings support a model whereby distinct pathways are activated by MTX in T cells and FLSs to inhibit NF-κB activation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.