ArticleArthritis and rheumatism2013
Angiogenesis in rheumatoid arthritis is fostered directly by toll-like receptor 5 ligation and indirectly through interleukin-17 induction.
Article in Arthritis and rheumatism, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 42 citations in OpenAlex.
- Notch ligands are biomarkers of anti-TNF response in RA patients.Angiogenesis · 2024Article
- Metabolic reprogramming by Syntenin-1 directs RA FLS and endothelial cell-mediated inflammation and angiogenesis.Cellular & molecular immunology · 2024Article
- HMGB1 and Toll-like receptors: potential therapeutic targets in autoimmune diseases.Molecular medicine (Cambridge, Mass.) · 2023Review
- Interplay of Chemokines Receptors, Toll-like Receptors, and Host Immunological Pathways.Biomedicines · 2023Review
- Review
- Metabolic regulation of RA macrophages is distinct from RA fibroblasts and blockade of glycolysis alleviates inflammatory phenotype in both cell types.Cellular and molecular life sciences : CMLS · 2021Article
- IRAK4 inhibition: a promising strategy for treating RA joint inflammation and bone erosion.Cellular & molecular immunology · 2021Article
- Transcriptome-wide association study identifies susceptibility genes for rheumatoid arthritis.Arthritis research & therapy · 2021Article
- Contribution of Toll-Like Receptors and the NLRP3 Inflammasome in Rheumatoid Arthritis Pathophysiology.ImmunoTargets and therapy · 2021Review
- Article
- When Innate Immunity Meets Angiogenesis-The Role of Toll-Like Receptors in Endothelial Cells and Pulmonary Hypertension.Frontiers in medicine · 2020Review
- Cross-Disease Innate Gene Signature: Emerging Diversity and Abundance in RA Comparing to SLE and SSc.Journal of immunology research · 2019Article
- Retinoic Acid Receptor-Related Receptor Alpha Ameliorates Autoimmune Arthritis via Inhibiting of Th17 Cells and Osteoclastogenesis.Frontiers in immunology · 2019Article
- [2-deoxyglucose inhibits angiogenesis of rheumatoid arthritis via activating AMPK pathway].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2018Article
- VLR Recognition of TLR5 Expands the Molecular Characterization of Protein Antigen Binding by Non-Ig-based Antibodies.Journal of molecular biology · 2018Article
- Protective Effect of Norcantharidin on Collagen-Induced Arthritis Rats.Chinese journal of integrative medicine · 2018Article
- Suppression of Th1 and Th17 Responses and Induction of Treg Responses by IL-18-Expressing Plasmid Gene Combined with IL-4 on Collagen-Induced Arthritis.BioMed research international · 2018Article
- Differential impact of obesity on the pathogenesis of RA or preclinical models is contingent on the disease status.Annals of the rheumatic diseases · 2017Article
- TLRs, future potential therapeutic targets for RA.Autoimmunity reviews · 2017Review
- Increased incidence of rheumatoid arthritis in multiple sclerosis: A nationwide cohort study.Medicine · 2016Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
objectiveTo examine the impact of Toll-like receptor 5 (TLR-5) on endothelial cell function in rheumatoid arthritis (RA) and vascularization in collagen-induced arthritis (CIA).
methodsEndothelial cell migration and tube formation assays were used to demonstrate the direct role of TLR-5 ligation in angiogenesis. Mice with CIA were treated with the TLR-5 agonist flagellin to document the effect of TLR-5 ligation in RA pathology. Vascularization in CIA was determined by immunohistochemical analysis and determination of cytokine levels in ankle joints. Spleen Th17 cells and joint interleukin-17 (IL-17) were quantified by fluorescence-activated cell sorting analysis and enzyme-linked immunosorbent assay. The development of Th17 cells induced by TLR-5 ligation was validated in RA peripheral blood mononuclear cells.
resultsLigation of TLR-5 to endogenous ligands expressed in RA synovial fluid contributed to endothelial cell infiltration and tube formation. Furthermore, treatment with flagellin after the onset of CIA exacerbated joint inflammation; in contrast, inflammation in control mice remained at a plateau phase. We showed that TLR-5-enhanced disease severity was attributable to Th17 cell differentiation and joint vascularization in CIA. Examination of the underlying mechanism using RA peripheral blood mononuclear cells documented that ligation of TLR-5 in myeloid cells and production of Th17-promoting cytokines were necessary for Th17 cell polarization. Additionally, we demonstrated that blockade of the IL-17 cascade markedly reduced endothelial cell migration activated by flagellin-conditioned medium, suggesting that TLR-5 ligation can mediate RA angiogenesis either directly by attracting endothelial cells or indirectly by fostering Th17 cell development.
conclusionOur data demonstrate a novel role for TLR-5 in RA angiogenesis; thus, TLR-5 may be a promising new target for RA treatment.
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