ArticleArthritis research & therapy2008
Extracellular heat shock protein 70 inhibits tumour necrosis factor-alpha induced proinflammatory mediator production in fibroblast-like synoviocytes.
Article in Arthritis research & therapy, 2008. 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, 92 citations in OpenAlex.
- Role of heat shock protein and cytokine expression as markers of clinical outcomes with glutamine-supplemented parenteral nutrition in surgical ICU patients.Clinical nutrition (Edinburgh, Scotland) · 2020Trial
- Radon balneotherapy in rheumatologic diseases: potential mechanisms and implications for cardiovascular autonomic control and inflammation.Clinical rheumatology · 2026Review
- Transcriptomic response to compressive force simulating orthodontic tooth movement in cultured porcine epithelial cell rests of Malassez.Odontology · 2026Article
- Reduced IgM natural autoantibody levels against heat shock proteins are associated with disease severity in juvenile idiopathic arthritis.Frontiers in immunology · 2026Article
- Exploring the Role of Heat Shock Proteins in Neuroimmune Modulation in Rheumatoid Arthritis: Insights from a Rat Model.International journal of molecular sciences · 2025Article
- Bone, dentin and cementum differentially influence the differentiation of osteoclast-like cells.Scientific reports · 2025Article
- Brevilin A inhibits IL‑17A‑induced inflammation in psoriasis by modulating HSP 70.Molecular medicine reports · 2025Article
- Dual roles ofFrontiers in immunology · 2025Article
- The function of carnosic acid in lipopolysaccharides-induced hepatic and intestinal inflammation in poultry.Poultry science · 2024Article
- Immunopeptides: immunomodulatory strategies and prospects for ocular immunity applications.Frontiers in immunology · 2024Review
- Heat Shock Proteins Alterations in Rheumatoid Arthritis.International journal of molecular sciences · 2022Review
- Methotrexate and theaflavin-3, 3'-digallate synergistically restore the balance between apoptosis and autophagy in synovial fibroblast of RA: an ex vivo approach with cultured human RA FLS.Inflammopharmacology · 2021Article
- Metabolic Reprogramming and Inflammatory Response Induced by D-Lactate in Bovine Fibroblast-Like Synoviocytes Depends on HIF-1 Activity.Frontiers in veterinary science · 2021Article
- D-Lactate Increases Cytokine Production in Bovine Fibroblast-Like Synoviocytes via MCT1 Uptake and the MAPK, PI3K/Akt, and NFκB Pathways.Animals : an open access journal from MDPI · 2020Article
- Heat Shock Protein 70 as a Double Agent Acting Inside and Outside the Cell: Insights into Autoimmunity.International journal of molecular sciences · 2020Review
- Circulating and Synovial Fluid Heat Shock Protein 70 Are Correlated with Severity in Knee Osteoarthritis.Cartilage · 2020Article
- Correlation between heat shock proteins, adiponectin, and T lymphocyte cytokine expression in type 2 diabetics.Cell stress & chaperones · 2018Article
- An overview of cytokines and heat shock response in polytraumatized patients.Cell stress & chaperones · 2018Review
- Cytokine, C-Reactive Protein, and Heat Shock Protein mRNA Expression Levels in Patients with Active Behçet's Uveitis.Medical science monitor : international medical journal of experimental and clinical research · 2018Article
- CD56bright cells respond to stimulation until very advanced age revealing increased expression of cellular protective proteins SIRT1, HSP70 and SOD2.Immunity & ageing : I & A · 2018Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionIt was recently suggested that heat shock protein (HSP)70, an intracellular protein, is a potential mediator of inflammatory disease when it is released into the extracellular compartment. Although elevated HSP70 levels have been identified in rheumatoid arthritis (RA) synovial tissues and RA synovial fluid compared with patients with osteoarthritis and healthy individuals, it remains unclear what role extracellular HSP70 plays in the pathogenesis of RA. This study was conducted to investigate the effects of extracellular HSP70 on the production of RA-associated cytokines in fibroblast-like synoviocytes from patients with RA and to elucidate the mechanisms involved.
methodsIL-6, IL-8 and monocyte chemoattractant protein (MCP)-1 levels in culture supernatants were measured using enzyme-linked immunosorbent assays. Activation of mitogen-activated protein kinases (MAPKs), such as extracellular signal-regulated protein kinases (ERKs), c-Jun amino-terminal kinase (JNK) and p38 MAPK, was detected using Western blotting. Nuclear translocation of nuclear factor-kappaB (NF-kappaB) and degradation of the inhibitory protein IkappaBalpha were examined using immunohistochemistry and Western blotting.
resultsHuman HSP70 downregulated IL-6, IL-8 and MCP-1 production in RA fibroblast-like synoviocytes induced by tumour necrosis factor (TNF)-alpha in a concentration dependent manner. HSP70 inhibited the activation of ERK, JNK and p38 MAPK in fibroblast-like synoviocytes stimulated by TNF-alpha. Furthermore, HSP70 also significantly inhibited nuclear translocation of nuclear factor-kappaB and degradation of IkappaBalpha induced by TNF-alpha.
conclusionExtracellular HSP70 has an anti-inflammatory effect on RA by downregulating production of IL-6, IL-8 and MCP-1 in fibroblast-like synoviocytes, which is mediated through inhibited activation of the MAPKs and NF-kappaB signal pathways.
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Registered trials
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.