ArticlePloS one2014
Metalloproteinase-dependent TLR2 ectodomain shedding is involved in soluble toll-like receptor 2 (sTLR2) production.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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The trial behind it
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Who cites it
32 citing papers in PubMed, 58 citations in OpenAlex.
- High intensity functional training versus traditional resistance training effects on inflammatory, metabolic, and physical outcomes in overweight men a randomized controlled trial.Scientific reports · 2026Trial
- The Soluble Form of Toll-Like Receptor 2 Is Elevated in Serum of Multiple Sclerosis Patients: A Novel Potential Disease Biomarker.Frontiers in immunology · 2018Trial
- Differential profiles of soluble and cellular toll like receptor (TLR)-2 and 4 in chronic periodontitis.PloS one · 2018Trial
- ADAM17 and its proteolytic targets in disease pathogenesis.The FEBS journal · 2026Review
- The role of soluble toll-like receptor-2 and 4 in children with pneumonia: a combined analysis of saliva and serum samples.Frontiers in immunology · 2026Article
- Article
- Effects of short-term sleep reduction and aerobic exercise on metabolism and inflammation in healthy adults.Current research in physiology · 2025Article
- TLR2 reprograms glucose metabolism in CD4Clinical rheumatology · 2024Article
- The Crucial Triad: Endothelial Glycocalyx, Oxidative Stress, and Inflammation in Cardiac Surgery-Exploring the Molecular Connections.International journal of molecular sciences · 2024Review
- Endothelial Dysfunction in Patients Undergoing Cardiac Surgery: A Narrative Review and Clinical Implications.Journal of cardiovascular development and disease · 2023Review
- The Presence of Psoriasis, Metabolic Syndrome and Their Combination Increases the Serum Levels of CRP and CD5L but Not sCD200R1 and sTLR2 in Participants.Journal of personalized medicine · 2022Article
- Lipopolysaccharide fromInternational journal of molecular sciences · 2022Article
- Immune Responses to IAV Infection and the Roles of L-Selectin and ADAM17 in Lymphocyte Homing.Pathogens (Basel, Switzerland) · 2022Review
- Alternative pre-mRNA splicing as a mechanism for terminating Toll-like Receptor signaling.Frontiers in immunology · 2022Review
- Potential Role of Soluble Toll-like Receptors 2 and 4 as Therapeutic Agents in Stroke and Brain Hemorrhage.International journal of molecular sciences · 2021Review
- Oral immune dysfunction is associated with the expansion of FOXP3Nature communications · 2021Article
- Association between serum soluble Toll-like receptor 2 and 4 and the risk of breast cancer.Molecular and clinical oncology · 2021Article
- Toll-Like Receptors: General Molecular and Structural Biology.Journal of immunology research · 2021Review
- The iRhom2/ADAM17 Axis Attenuates Bacterial Uptake by Phagocytes in a Cell Autonomous Manner.International journal of molecular sciences · 2020Article
- Immune Checkpoint Axes Are Dysregulated in Patients With Alcoholic Hepatitis.Hepatology communications · 2020Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Toll-like receptor (TLR) 2, a type I membrane receptor that plays a key role in innate immunity, recognizes conserved molecules in pathogens, and triggering an inflammatory response. It has been associated with inflammatory and autoimmune diseases. Soluble TLR2 (sTLR2) variants have been identified in human body fluids, and the TLR2 ectodomain can negatively regulate TLR2 activation by behaving as a decoy receptor. sTLR2 generation does not involve alternative splicing mechanisms, indicating that this process might involve a post-translational modification of the full-length receptor; however, the specific mechanism has not been studied. Using CD14+ peripheral human monocytes and the THP-1 monocytic leukemia-derived cell line, we confirm that sTLR2 generation increases upon treatment with pro-inflammatory agents and requires a post-translational mechanism. We also find that the constitutive and ligand-induced release of sTLR2 is sensitive to pharmacological metalloproteinase activator and inhibitors leading us to conclude that metalloproteinase TLR2 shedding contributes to soluble receptor production. By expressing human TLR2 in ADAM10- or ADAM17-deficient MEF cells, we find both enzymes to be implicated in TLR2 ectodomain shedding. Moreover, using a deletion mutant of the TLR2 juxtamembrane region, we demonstrate that this domain is required for sTLR2 generation. Functional analysis suggests that sTLR2 generated by metalloproteinase activation inhibitsTLR2-induced cytokine production by this monocytic leukemia-derived cell line. The identification of the mechanisms involved in regulating the availability of soluble TLR2 ectodomain and cell surface receptors may contribute further research on TLR2-mediated processes in innate immunity and inflammatory disorders.
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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.