ArticlePloS one2019
Upregulation of sphingosine-1-phosphate receptor 3 on fibroblast-like synoviocytes is associated with the development of collagen-induced arthritis via increased interleukin-6 production.
Article in PloS one, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 29 citations in OpenAlex.
- Integrative mass spectrometry-driven multi-omics and single cell technologies in ankylosing spondylitis: insights into pathogenesis, biomarker discovery, and precision medicine.Journal of translational autoimmunity · 2025Review
- The regulatory functions of G protein-coupled receptors signaling pathways in B cell differentiation and development contributing to autoimmune diseases.Cell & bioscience · 2025Review
- Metabolites as regulators of autoimmune diseases.Frontiers in immunology · 2025Review
- Broad and diverse roles of sphingosine-1-phosphate/sphingosine-1-phosphate receptors in the prostate.iScience · 2024Article
- Blocking the Sphingosine-1-Phosphate Receptor 2 (S1PInternational journal of molecular sciences · 2024Article
- Article
- S1P/S1PR signaling pathway advancements in autoimmune diseases.Biomolecules & biomedicine · 2023Review
- Silence of S1PR4 Represses the Activation of Fibroblast-like Synoviocytes by Regulating IL-17/STAT3 Signaling Pathway.Inflammation · 2023Article
- Ceramides in Autoimmune Rheumatic Diseases: Existing Evidence and Therapeutic Considerations for Diet as an Anticeramide Treatment.Nutrients · 2023Review
- EGFR blocker lapatinib inhibits the synthesis of matrix metalloproteinases from synovial fibroblasts.Turkish journal of medical sciences · 2022Article
- Comparison of immune cells and diagnostic markers between spondyloarthritis and rheumatoid arthritis by bioinformatics analysis.Journal of translational medicine · 2022Article
- Review article: the sphingosine 1 phosphate/sphingosine 1 phosphate receptor axis - a unique therapeutic target in inflammatory bowel disease.Alimentary pharmacology & therapeutics · 2022Review
- Lipids in Liver Failure Syndromes: A Focus on Eicosanoids, Specialized Pro-Resolving Lipid Mediators and Lysophospholipids.Frontiers in immunology · 2022Review
- Lipidomic Profiling in Synovial Tissue.Frontiers in medicine · 2022Review
- Article
- Bioactive sphingolipids: Advancements and contributions from the laboratory of Dr. Lina M. Obeid.Cellular signalling · 2021Review
- A bioavailable form of curcumin, in combination with vitamin-D- and omega-3-enriched diet, modifies disease onset and outcomes in a murine model of collagen-induced arthritis.Arthritis research & therapy · 2021Article
- Functional Lipids in Autoimmune Inflammatory Diseases.International journal of molecular sciences · 2020Review
- Anti-Inflammatory Effect of Geniposide on Regulating the Functions of Rheumatoid Arthritis Synovial Fibroblasts via Inhibiting Sphingosine-1-Phosphate Receptors1/3 Coupling Gαi/Gαs Conversion.Frontiers in pharmacology · 2020Article
- S1P promotes IL-6 expression in osteoblasts through the PI3K, MEK/ERK and NF-κB signaling pathways.International journal of medical sciences · 2020Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundSphingosine-1-phosphate receptor 3 (S1P3) is one of five receptors for sphingosine-1-phosphate (S1P). S1P/S1P3 signaling is involved in numerous physiological and pathological processes including bone metabolism, sepsis, cancer, and immunity. In rheumatoid arthritis (RA), fibroblast-like synoviocytes (FLSs) are activated by several factors and promote abundant proinflammatory cytokine production and bone destruction. The aim of this study was to investigate whether S1P3 is associated with the development of autoimmune arthritis and the pathogenic function of FLSs.
methodsWild-type (WT) and S1P3 knockout (S1P3-KO) collagen-induced arthritis (CIA) mice were evaluated with respect to clinical and histological disease severity, along with the levels of anti-collagen antibodies and expression of tumor necrosis factor-α (TNFα) and interleukin-6 (IL-6). S1P3 expression in the synovium was analyzed by real-time reverse-transcription polymerase chain reaction (RT-PCR) and immunofluorescence staining. FLSs isolated from CIA mice were activated with TNFα and S1P3 expression was analyzed by real-time RT-PCR. The role of S1P/S1P3 signaling in activated and non-activated FLSs was investigated by measuring cell proliferation and cyto/chemokine production by real-time RT-PCR and/or enzyme-linked immunosorbent assay.
resultsClinical and histological scores, and synovial IL-6 expression were significantly lower in S1P3-KO mice with CIA than in WT mice. Arthritic synovia had higher S1P3 expression than intact synovia and FLSs in arthritic joints expressed S1P3 in vivo. Primary cultured FLSs produced IL-6 in a time-dependent manner in response to S1P stimulation and exhibited higher levels of S1P3 expression after activation with TNFα. S1P3-induced production of IL-6 and MMP-3 was increased in FLSs pre-activated with TNFα.
conclusionIn this study, we demonstrated that S1P3 expression is associated with the development of autoimmune arthritis via inflammation-induced increases in S1P/S1P3 signaling that increase production of IL-6 in FLSs. Inhibition of S1P/S1P3 signaling could open the door to the development of new therapies for RA.
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