ArticlePloS one2016
A Cytokine Signalling Network for the Regulation of Inducible Nitric Oxide Synthase Expression in Rheumatoid Arthritis.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 84 citations in OpenAlex.
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- Aging associated immunosenescence in rheumatoid arthritis identified by machine learning and single cell profiling.Scientific reports · 2025Article
- Inflammatory microenvironment-responsive MR imaging contrast agents.Nanomedicine (London, England) · 2025Review
- Genetic factors may load the gun, but environmental factors pull the trigger: MedDiet and DII in rheumatoid arthritis.Frontiers in nutrition · 2025Review
- Salt Behind the Scenes of Systemic Lupus Erythematosus and Rheumatoid Arthritis.Current nutrition reports · 2023Review
- Phytoceramide Alleviates the Carrageenan/Kaolin-Induced Arthritic Symptoms by Modulation of Inflammation.Biomolecules & therapeutics · 2023Article
- Nitric Oxide Synthases in Rheumatoid Arthritis.Molecules (Basel, Switzerland) · 2023Review
- The Behavioral and Neurochemical Changes Induced by Boldenone and/or Tramadol in Adult Male Rats.Neurochemical research · 2023Article
- Emerging role of mesenchymal stem/stromal cells (MSCs) and MSCs-derived exosomes in bone- and joint-associated musculoskeletal disorders: a new frontier.European journal of medical research · 2023Review
- Identification of immunological characterization and Anoikis-related molecular clusters in rheumatoid arthritis.Frontiers in molecular biosciences · 2023Article
- P19 a Parthenin Analog Induces Cell Lineage Dependent Apoptotic and Immunomodulatory Signaling in Acute Lymphoid Leukemia Cells.International journal of molecular and cellular medicine · 2023Article
- IFN-γ lowers tumor growth by increasing glycolysis and lactate production in a nitric oxide-dependent manner: implications for cancer immunotherapy.Frontiers in immunology · 2023Article
- Development of Methotrexate Complexes Endowed with New Biological Properties Envisioned for Musculoskeletal Regeneration in Rheumatoid Arthritis Environments.International journal of molecular sciences · 2022Article
- Rho GTPase signaling in rheumatic diseases.iScience · 2022Review
- The essential anti-angiogenic strategies in cartilage engineering and osteoarthritic cartilage repair.Cellular and molecular life sciences : CMLS · 2022Review
- Gintonin regulates inflammation in human IL-1β-stimulated fibroblast-like synoviocytes and carrageenan/kaolin-induced arthritis in rats through LPAR2.Journal of ginseng research · 2021Article
- Inhibitory activity of gintonin on inflammation in human IL-1β-stimulated fibroblast-like synoviocytes and collagen-induced arthritis in mice.Journal of ginseng research · 2021Article
- Mesenchymal stem/stromal cells as a valuable source for the treatment of immune-mediated disorders.Stem cell research & therapy · 2021Review
- Inhibitory effects of cynaropicrin and related sesquiterpene lactones from leaves of artichoke (Cynara scolymus L.) on induction of iNOS in RAW264.7 cells and its high-affinity proteins.Journal of natural medicines · 2021Article
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3 authors at 2 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
In rheumatoid arthritis (RA), nitric oxide (NO) is implicated in inflammation, angiogenesis and tissue destruction. The enzyme inducible nitric oxide synthase (iNOS) is responsible for the localised over-production of NO in the synovial joints affected by RA. The pro- and anti-inflammatory cytokines stimulate the synovial macrophages and the fibroblast-like synoviocytes to express iNOS. Therefore, the cytokine signalling network underlying the regulation of iNOS is essential to understand the pathophysiology of the disease. By using information from the literature, we have constructed, for the first time, the cytokine signalling network involved in the regulation of iNOS expression. Using the differential expression patterns obtained by re-analysing the microarray data on the RA synovium and the synovial macrophages available in the Gene Expression Omnibus (GEO) database, we aimed to establish the role played by the network genes towards iNOS regulation in the RA synovium. Our analysis reveals that the network genes belonging to interferon (IFN) and interleukin-10 (IL-10) pathways are always up-regulated in the RA synovium whereas the genes which are part of the anti-inflammatory transforming growth factor-beta (TGF-β) signalling pathway are mostly down-regulated. We observed a consistent up-regulation of the transcription factor signal transducers and activators of transcription 1 (STAT1) in the RA synovium and the macrophages. Interestingly, we found a consistent up-regulation of the iNOS interacting protein ras-related C3 botulinum toxin substrate 2 (RAC2) in the RA synovium as well as the macrophages. Importantly, we have constructed a model to explain the impact of IFN and IL-10 pathways on Rac2-iNOS interaction leading to over-production of NO and thereby causing chronic inflammation in the RA synovium. The interplay between STAT1 and RAC2 in the regulation of NO could have implications for the identification of therapeutic targets for RA.
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