ArticleScientific reports2019
Activation of Toll-like Receptor 2 (TLR2) induces Interleukin-6 trans-signaling.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 64 citations in OpenAlex.
- Monocyte markers correlate with immune and neuronal brain changes in REM sleep behavior disorder.Proceedings of the National Academy of Sciences of the United States of America · 2021Trial
- Brucella outer membrane protein 16 induces trophoblast pyroptosis via rewiring IL-6 trans-signaling and caspase-3/GSDME axis.PLoS neglected tropical diseases · 2026Article
- AgeFrontiers in pediatrics · 2026Article
- Prediction of the risk of transplant rejection based on RNA sequencing data of PBMCs before transplantation.Scientific reports · 2025Article
- SPP1 + macrophages cause exhaustion of tumor-specific T cells in liver metastases.Nature communications · 2025Article
- A novel TLR4 accessory molecule drives hepatic oncogenesis through tumor-associated macrophages.Cancer letters · 2025Article
- Deciphering Pectin: A Comprehensive Overview of Its Origins, Processing, and Promising Utility.ACS omega · 2025Review
- IL-6 Signaling in Immunopathology: From Basic Biology to Selective Therapeutic Intervention.ImmunoTargets and therapy · 2025Review
- Toll-like receptor agonists as cancer vaccine adjuvants.Human vaccines & immunotherapeutics · 2024Review
- Exploring the hub Genes and Potential Mechanisms of Complement system-related Genes in Parkinson Disease: Based on Transcriptome Sequencing and Mendelian Randomization.Journal of molecular neuroscience : MN · 2024Article
- A Paradoxical Tumor Antigen Specific Response in the Liver.bioRxiv : the preprint server for biology · 2024Article
- Development of an iPSC-derived tissue-resident macrophage-based platform for the in vitro immunocompatibility assessment of human tissue engineered matrices.Scientific reports · 2024Article
- Significance of extracellular vesicles in orchestration of immune responses inFrontiers in cellular and infection microbiology · 2024Review
- Complete spectrum of adverse events associated with chimeric antigen receptor (CAR)-T cell therapies.Journal of biomedical science · 2023Review
- An Update on Toll-like Receptor 2, Its Function and Dimerization in Pro- and Anti-Inflammatory Processes.International journal of molecular sciences · 2023Review
- Single-cell deep phenotyping of cytokine release unmasks stimulation-specific biological signatures and distinct secretion dynamics.Cell reports methods · 2023Article
- The role of TLR2 in exercise-induced immunomodulation in normal weight individuals.Scientific reports · 2023Article
- Myeloid cells protect corneal nerves against sterile injury through negative-feedback regulation of TLR2-IL-6 axis.Journal of neuroinflammation · 2023Article
- Toll-like Receptor 4 in Acute Kidney Injury.International journal of molecular sciences · 2023Review
- Review
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Signaling of the pleiotropic cytokine Interleukin-6 (IL-6) via its soluble IL-6R (sIL-6R) has been termed trans-signaling and is thought to be responsible for the pro-inflammatory properties of IL-6. The sIL-6R can be generated by alternative mRNA splicing or proteolytic cleavage of the membrane-bound IL-6R. However, which stimuli induce sIL-6R release and which endogenous signaling pathways are required for this process is poorly understood. Here, we show that activation of Toll-like receptor 2 (TLR2) on primary human peripheral blood mononuclear cells (PBMCs) and on the monocytic cell line THP-1 induces expression and secretion of IL-6 and the generation of sIL-6R. We show by flow cytometry that monocytes are a PBMC subset that expresses TLR2 in conjunction with the IL-6R and are the major cellular source for both IL-6 and sIL-6R. Mechanistically, we find that the metalloproteases ADAM10 and ADAM17 are responsible for cleavage of the IL-6R and therefore sIL-6R generation. Finally, we identify the Extracellular-signal Regulated Kinase (ERK) cascade as a critical pathway that differentially regulates both IL-6 and sIL-6R generation in monocytes.
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