ArticleThe Journal of biological chemistry2016
The Anti-inflammatory Protein TSG-6 Regulates Chemokine Function by Inhibiting Chemokine/Glycosaminoglycan Interactions.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
68 citing papers in PubMed, 1 synthesis or guideline pooled it, 109 citations in OpenAlex.
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- Microarray Analysis of Differentially Expressed Genes in Peripheral Blood of Postpartum Women with Gestational Diabetes Mellitus and Type 2 Diabetes.Life (Basel, Switzerland) · 2025Article
- Disrupting SARS-CoV-2 Spike-ACE2 Interactions via Glycosaminoglycans in a Pseudoviral Study of Heparan Sulfate and Enoxaparin.Biomolecules · 2025Article
- Potential drug targets for ovarian cancer identified through Mendelian randomization and colocalization analysis.Journal of ovarian research · 2025Article
- Effects of Release of TSG-6 from Heparin Hydrogels on Supraspinatus Muscle Regeneration.Tissue engineering. Part A · 2025Article
- Designing a CXCL8-hsa chimera as potential immunmodulator of the tumor micro-environment.Frontiers in immunology · 2025Article
- TSG-6 expression distinguishes rejected and non-rejected human lung transplants: a retrospective study.Frontiers in immunology · 2025Article
- TSG-6 promotes healing of critical-sized bone defects in mice.Frontiers in immunology · 2025Article
- Endogenous TSG-6 modulates corneal inflammation following chemical injury.The ocular surface · 2024Article
- Chemokines form complex signals during inflammation and disease that can be decoded by extracellular matrix proteoglycans.Science signaling · 2023Article
- Human Synovial Mesenchymal Stem Cells Expressed Immunoregulatory Factors IDO and TSG6 in a Context of Arthritis Mediated by Alphaviruses.International journal of molecular sciences · 2023Article
- A cohort-based study of host gene expression: tumor suppressor and innate immune/inflammatory pathways associated with the HIV reservoir size.PLoS pathogens · 2023Article
- IL4I1-catalyzed tryptophan metabolites mediate the anti-inflammatory function of cytokine-primed human muscle stem cells.Cell death discovery · 2023Article
- The chemokines CXCL8 and CXCL12: molecular and functional properties, role in disease and efforts towards pharmacological intervention.Cellular & molecular immunology · 2023Review
- Tumor Necrosis Factor (TNF)-α-Stimulated Gene 6 (TSG-6): A Promising Immunomodulatory Target in Acute Neurodegenerative Diseases.International journal of molecular sciences · 2023Review
- Use of Mesenchymal Stem Cells in Crohn's Disease and Perianal Fistulas: A Narrative Review.Current stem cell research & therapy · 2023Review
- Neutrophil infiltration associated genes on the prognosis and tumor immune microenvironment of lung adenocarcinoma.Frontiers in immunology · 2023Article
- CXCL17 binds efficaciously to glycosaminoglycans with the potential to modulate chemokine signaling.Frontiers in immunology · 2023Article
8 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 2 countries.
Funding
Abstract
TNF-stimulated gene-6 (TSG-6) is a multifunctional protein secreted in response to pro-inflammatory stimuli by a wide range of cells, including neutrophils, monocytes, and endothelial cells. It has been shown to mediate anti-inflammatory and protective effects when administered in disease models, in part, by reducing neutrophil infiltration. Human TSG-6 inhibits neutrophil migration by binding CXCL8 through its Link module (Link_TSG6) and interfering with the presentation of CXCL8 on cell-surface glycosaminoglycans (GAGs), an interaction that is vital for the function of many chemokines. TSG-6 was also found to interact with chemokines CXCL11 and CCL5, suggesting the possibility that it may function as a broad specificity chemokine-binding protein, functionally similar to those encoded by viruses. This study was therefore undertaken to explore the ability of TSG-6 to regulate the function of other chemokines. Herein, we demonstrate that Link_TSG6 binds chemokines from both the CXC and CC families, including CXCL4, CXCL12, CCL2, CCL5, CCL7, CCL19, CCL21, and CCL27. We also show that the Link_TSG6-binding sites on chemokines overlap with chemokine GAG-binding sites, and that the affinities of Link_TSG6 for these chemokines (KD values 1-85 nm) broadly correlate with chemokine-GAG affinities. Link_TSG6 also inhibits chemokine presentation on endothelial cells not only through a direct interaction with chemokines but also by binding and therefore masking the availability of GAGs. Along with previous work, these findings suggest that TSG-6 functions as a pluripotent regulator of chemokines by modulating chemokine/GAG interactions, which may be a major mechanism by which TSG-6 produces its anti-inflammatory effects in vivo.
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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.