ArticleArthritis research & therapy2014
Methotrexate induces production of IL-1 and IL-6 in the monocytic cell line U937.
Article in Arthritis research & therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 66 citations in OpenAlex.
- Trial
- Beyond the Prevention of Anti-drug Antibody Formation with Uricase Therapy: Mechanistic Roles of DMARDs in Modifying Gout Flare Risk.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- Reticuline alleviates rheumatoid arthritis by suppressing the JAK/STAT signaling pathway.Clinical rheumatology · 2026Article
- Methotrexate for Osteoarthritis: What Does the Evidence Say?Drugs & aging · 2026Review
- Production optimization andFrontiers in microbiology · 2026Article
- The Role and Mechanistic Effects of Methotrexate in the Treatment of Rheumatoid Arthritis.European journal of rheumatology · 2025Article
- Methotrexate osteopathy in rheumatoid arthritis.Rheumatology international · 2025Review
- 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
- Cinnamic acid mitigates methotrexate-induced lung fibrosis in rats: comparative study with pirfenidone.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- L-methionine protects against nephrotoxicity induced by methotrexate through modulation of redox status and inflammation.Redox report : communications in free radical research · 2023Article
- In Vitro and In Silico Analysis of the Anticancer Effects of Eurycomanone and Eurycomalactone fromPlants (Basel, Switzerland) · 2023Article
- Bilirubin gates the TRPM2 channel as a direct agonist to exacerbate ischemic brain damage.Neuron · 2023Article
- Investigating the correlation of the NF-κB and FoxP3 gene expression with the plasma levels of pro- and anti-inflammatory cytokines in rheumatoid arthritis patients.Clinical rheumatology · 2023Article
- Serum Levels of Selected IL-1 Family Cytokines in Patients with Morphea.Journal of clinical medicine · 2022Article
- Macrophage Dysfunction in Autoimmune Rheumatic Diseases and Atherosclerosis.International journal of molecular sciences · 2022Review
- Monocytes and Macrophages in Spondyloarthritis: Functional Roles and Effects of Current Therapies.Cells · 2022Review
- Methotrexate Treatment Suppresses Monocytes in Nonresponders to Pneumococcal Conjugate Vaccine in Rheumatoid Arthritis Patients.Journal of immunology research · 2022Article
- Article
- Could IL-1β, IL-6, IFN-γ, and sP-selectin serum levels be considered as objective and quantifiable markers of rheumatoid arthritis severity and activity?Reumatologia · 2022Article
- Clinical and Radiological Characterization of Patients with Immobilizing and Progressive Stress Fractures in Methotrexate Osteopathy.Calcified tissue international · 2021Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionMethotrexate (MTX) has been for decades a standard treatment in a wide range of conditions, from malignancies to rheumatoid arthritis (RA). Despite this long experience, the mechanisms of action of MTX remain incompletely understood. Reported immunologic effects of MTX include induction of increased production of some cytokines, an effect that seems to be at odds with the generally anti-inflammatory effects of this drug in diseases like RA. To further elucidate these immune activities, we examined effects of MTX on the human monocytic cell line U937.
methodsThe U937 cell line was treated in vitro with pharmacologic-range concentrations of MTX and effects on production of interleukin (IL)-1, IL-6 and TNF alpha were measured. Changes in gene expression for IL-1 and IL-6 and specificities in the Jun-N-terminal kinase (JNK) signaling pathway including JNK 1, JNK2, JUN and FOS were also determined. The contribution of NF-kB, folate and adenosine pathways to the observed effects was determined by adding appropriate inhibitors to the MTX cultures.
resultsMTX mediated a dose-dependent increase in IL-1 and IL-6 in U937 cells, as measured by secreted proteins and levels of gene expression. The increased cytokine expression was inhibited by addition of parthenolide and folinic acid, but not by caffeine and theophylline, suggesting that NF-kB and folates, but not adenosine, were involved in mediating the observed effects. When U937 cells were cultured with MTX, upregulated expression of JUN and FOS, but not JNK 1 or 2, also was observed.
conclusionsMTX induces expression of proinflammatory cytokines in U937 monocytic cells. These effects might mediate the known toxicities of MTX including pneumonitis, mucositis and decreased bone mineral density.
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