ArticleArthritis and rheumatism2012
Glycoprotein 96 perpetuates the persistent inflammation of rheumatoid arthritis.
Article in Arthritis and rheumatism, 2012. 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, 24 citations in OpenAlex.
- Expression of circulating GRP78 and gp96, endoplasmic reticulum stress-related proteins, in menstrual and bladder pain sensitivity.Scientific reports · 2026Article
- Cell- and Serum-Derived Proteins Act as DAMPs to Activate RAW 264.7 Macrophage-like Cells on Silicone Implants.ACS biomaterials science & engineering · 2024Article
- The biology and inhibition of glucose-regulated protein 94/gp96.Medicinal research reviews · 2022Review
- Glycoprotein 96 in Peritoneal Dialysis Effluent-Derived Extracellular Vesicles: A Tool for Evaluating Peritoneal Transport Properties and Inflammatory Status.Frontiers in immunology · 2022Article
- Extracellular gp96 is a crucial mediator for driving immune hyperactivation and liver damage.Scientific reports · 2020Article
- Monocyte and haematopoietic progenitor reprogramming as common mechanism underlying chronic inflammatory and cardiovascular diseases.European heart journal · 2018Review
- The Role of Macrophages in the Response to TNF Inhibition in Experimental Arthritis.Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- Association of Increased F4/80Arthritis & rheumatology (Hoboken, N.J.) · 2017Article
- Article
- SNAPIN is critical for lysosomal acidification and autophagosome maturation in macrophages.Autophagy · 2017Article
- Molecular mechanisms of regulation of Toll-like receptor signaling.Journal of leukocyte biology · 2016Review
- Deletion of calponin 2 in macrophages attenuates the severity of inflammatory arthritis in mice.American journal of physiology. Cell physiology · 2016Article
- Toll-like receptors and chronic inflammation in rheumatic diseases: new developments.Nature reviews. Rheumatology · 2016Review
- The interaction of lubricin/proteoglycan 4 (PRG4) with toll-like receptors 2 and 4: an anti-inflammatory role of PRG4 in synovial fluid.Arthritis research & therapy · 2015Article
- CD11c-mediated deletion of Flip promotes autoreactivity and inflammatory arthritis.Nature communications · 2015Article
- TLR2 and TLR4 in autoimmune diseases: a comprehensive review.Clinical reviews in allergy & immunology · 2014Review
- Fas signaling in macrophages promotes chronicity in K/BxN serum-induced arthritis.Arthritis & rheumatology (Hoboken, N.J.) · 2014Article
- TLR2 deletion promotes arthritis through reduction of IL-10.Journal of leukocyte biology · 2013Article
- The role of glycoprotein 96 in the persistent inflammation of rheumatoid arthritis.Archives of biochemistry and biophysics · 2013Review
- Human α1-Antitrypsin Binds to Heat-Shock Protein gp96 and Protects from Endogenous gp96-Mediated Injury In vivo.Frontiers in immunology · 2013Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
objectiveThe mechanisms that contribute to the persistent activation of macrophages in rheumatoid arthritis (RA) are incompletely understood. The aim of this study was to determine the contribution of endogenous gp96 in Toll-like receptor (TLR)-mediated macrophage activation in RA.
methodsRA synovial fluid was used to activate macrophages and HEK-TLR-2 and HEK-TLR-4 cells. Neutralizing antibodies to TLR-2, TLR-4, and gp96 were used to inhibit activation. RA synovial fluid macrophages were isolated by CD14 negative selection. Cell activation was measured by the expression of tumor necrosis factor α (TNFα) or interleukin-8 messenger RNA. Arthritis was induced in mice by K/BxN serum transfer. The expression of gp96 was determined by immunoblot analysis, enzyme-linked immunosorbent assay, and immunohistochemistry. Arthritis was treated with neutralizing anti-gp96 antiserum or control serum.
resultsRA synovial fluid induced the activation of macrophages and HEK-TLR-2 and HEK-TLR-4 cells. RA synovial fluid-induced macrophage and HEK-TLR-2 activation was suppressed by neutralizing anti-gp96 antibodies only in the presence of high (>800 ng/ml) rather than low (<400 ng/ml) concentrations of gp96. Neutralization of RA synovial fluid macrophage cell surface gp96 inhibited the constitutive expression of TNFα. Supporting the role of gp96 in RA, joint tissue gp96 expression was induced in mice with the K/BxN serum-induced arthritis, and neutralizing antibodies to gp96 ameliorated joint inflammation, as determined by clinical and histologic examination.
conclusionThese observations support the notion that gp96 plays a role as an endogenous TLR-2 ligand in RA and identify the TLR-2 pathway as a therapeutic target.
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Registered trials
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