ArticleThe Journal of biological chemistry2011
TSG-6 protein, a negative regulator of inflammatory arthritis, forms a ternary complex with murine mast cell tryptases and heparin.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 41 citations in OpenAlex.
- Kynurenic Acid Analog Attenuates the Production of Tumor Necrosis Factor-α, Calgranulins (S100A 8/9 and S100A 12), and the Secretion of HNP1-3, and Stimulates the Production of Tumor Necrosis Factor-Stimulated Gene-6 (TSG-6) but Does Not Alter IL-17 Levels in Whole-Blood Cultures of Patients with Spondyloarthritis.International journal of molecular sciences · 2025Article
- Endogenous TSG-6 modulates corneal inflammation following chemical injury.The ocular surface · 2024Article
- TSG6 hyaluronan matrix remodeling dampens the inflammatory response during colitis.Matrix biology : journal of the International Society for Matrix Biology · 2023Article
- Crosstalk between CD4 T cells and synovial fibroblasts from human arthritic joints promotes hyaluronan-dependent leukocyte adhesion and inflammatory cytokine expression in vitro.Matrix biology plus · 2022Article
- Tumor necrosis factor-alpha stimulated gene-6: A biomarker reflecting disease activity in rheumatoid arthritis.Journal of clinical laboratory analysis · 2022Article
- Early prediction of clinical response to anti-TNF treatment using multi-omics and machine learning in rheumatoid arthritis.Rheumatology (Oxford, England) · 2022Article
- TSG-6 Is Weakly Chondroprotective in Murine OA but Does not Account for FGF2-Mediated Joint Protection.ACR open rheumatology · 2020Article
- In vitro analysis of the role of tumor necrosis factor‑stimulated gene‑6 in keloid.Molecular medicine reports · 2019Article
- Gonadotropin regulation of ankyrin-repeat and SOCS-box protein 9 (ASB9) in ovarian follicles and identification of binding partners.PloS one · 2019Article
- Emerging Roles of Tumor Necrosis Factor-Stimulated Gene-6 in the Pathophysiology and Treatment of Atherosclerosis.International journal of molecular sciences · 2018Review
- TSG-6 - a double-edged sword for osteoarthritis (OA).Osteoarthritis and cartilage · 2018Article
- The role of TSG-6 and uroplakin III in bladder pain syndrome/ interstitial cystitis in rats and humans.Iranian journal of basic medical sciences · 2017Article
- Tumor Necrosis Factor-stimulated Gene-6 (TSG-6) Is Constitutively Expressed in Adult Central Nervous System (CNS) and Associated with Astrocyte-mediated Glial Scar Formation following Spinal Cord Injury.The Journal of biological chemistry · 2016Article
- The Anti-inflammatory Protein TSG-6 Regulates Chemokine Function by Inhibiting Chemokine/Glycosaminoglycan Interactions.The Journal of biological chemistry · 2016Article
- Scalable Production of a Multifunctional Protein (TSG-6) That Aggregates with Itself and the CHO Cells That Synthesize It.PloS one · 2016Article
- Hyaluronan cable formation by ocular trabecular meshwork cells.Experimental eye research · 2015Article
- Response to Infliximab in Crohn's Disease: Genetic Analysis Supporting Expression Profile.Mediators of inflammation · 2015Article
- Article
- TSG-6 inhibits neutrophil migration via direct interaction with the chemokine CXCL8.Journal of immunology (Baltimore, Md. : 1950) · 2014Article
- A refined model for the TSG-6 link module in complex with hyaluronan: use of defined oligosaccharides to probe structure and function.The Journal of biological chemistry · 2014Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
TSG-6 (TNF-α-stimulated gene/protein 6), a hyaluronan (HA)-binding protein, has been implicated in the negative regulation of inflammatory tissue destruction. However, little is known about the tissue/cell-specific expression of TSG-6 in inflammatory processes, due to the lack of appropriate reagents for the detection of this protein in vivo. Here, we report on the development of a highly sensitive detection system and its use in cartilage proteoglycan (aggrecan)-induced arthritis, an autoimmune murine model of rheumatoid arthritis. We found significant correlation between serum concentrations of TSG-6 and arthritis severity throughout the disease process, making TSG-6 a better biomarker of inflammation than any of the other arthritis-related cytokines measured in this study. TSG-6 was present in arthritic joint tissue extracts together with the heavy chains of inter-α-inhibitor (IαI). Whereas TSG-6 was broadly detectable in arthritic synovial tissue, the highest level of TSG-6 was co-localized with tryptases in the heparin-containing secretory granules of mast cells. In vitro, TSG-6 formed complexes with the tryptases murine mast cell protease-6 and -7 via either heparin or HA. In vivo TSG-6-tryptase association could also be detected in arthritic joint extracts by co-immunoprecipitation. TSG-6 has been reported to suppress inflammatory tissue destruction by enhancing the serine protease-inhibitory activity of IαI against plasmin. TSG-6 achieves this by transferring heavy chains from IαI to HA, thus liberating the active bikunin subunit of IαI. Because bikunin is also present in mast cell granules, we propose that TSG-6 can promote inhibition of tryptase activity via a mechanism similar to inhibition of plasmin.
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Registered trials
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