ArticleThe Journal of biological chemistry2016
Different Soluble Forms of the Interleukin-6 Family Signal Transducer gp130 Fine-tune the Blockade of Interleukin-6 Trans-signaling.
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 58 papers.
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Who cites it
58 citing papers in PubMed, 91 citations in OpenAlex.
- Refining therapeutic targeting of interleukin-6 by signalling mode selectivity.Nature reviews. Drug discovery · 2026Review
- Therapeutic Effects and Mechanisms of Olfactory Training in a Murine Model of Olfactory Dysfunction.Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery · 2026Article
- Loss of cold shock domain-containing protein E1 (CSDE1) function enhances mRNA stability of interleukin-6 and promotes malignant transformation in endometrial cancer cells.Cell communication and signaling : CCS · 2026Article
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- IL‑6: A key player in the EGFR‑TKI‑resistant tumor microenvironment and its therapeutic implications (Review).International journal of oncology · 2026Review
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- Soluble IL-2R: A potential therapeutic target for mitochondrial dysfunction in post-COVID fatigue syndrome.Clinical and translational medicine · 2025Article
- Recent cannabis use affects the association between baseline immune markers and long-term outcomes in psychosis.Translational psychiatry · 2025Article
- Alternative Splicing at the Crossroad of Inflammatory Bowel Diseases and Colitis-Associated Colon Cancer.Cancers · 2025Review
- IL-6 Signaling in Immunopathology: From Basic Biology to Selective Therapeutic Intervention.ImmunoTargets and therapy · 2025Review
- Proteomic Alterations in Retinal Müller Glial Cells Lacking Interleukin-6 Receptor: A Comprehensive Analysis.Investigative ophthalmology & visual science · 2024Article
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- Myokines: metabolic regulation in obesity and type 2 diabetes.Life metabolism · 2024Review
- Role of microbiota in radiation-induced small-bowel damage.Journal of radiation research · 2024Article
- Alternative splicing of modulatory immune receptors in T lymphocytes: a newly identified and targetable mechanism for anticancer immunotherapy.Frontiers in immunology · 2024Review
- Long-term increase in soluble interleukin-6 receptor levels in convalescents after mild COVID-19 infection.Frontiers in immunology · 2024Article
- IL-6 Blockade in Cytokine Storm Syndromes.Advances in experimental medicine and biology · 2024Review
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- Differential Roles of Interleukin-6 in Severe Acute Respiratory Syndrome-Coronavirus-2 Infection and Cardiometabolic Diseases.Cardiology discovery · 2023Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Soluble forms of the IL-6 receptor (sIL-6R) bind to the cytokine IL-6 with similar affinity as the membrane-bound IL-6R. IL-6·sIL-6R complexes initiate IL-6 trans-signaling via activation of the ubiquitously expressed membrane-bound β-receptor glycoprotein 130 (gp130). Inhibition of IL-6 trans-signaling has been shown to be favorable in numerous inflammatory diseases. Furthermore, different soluble forms of gp130 (sgp130) exist that, together with the sIL-6R, are thought to form a buffer for IL-6 in the blood. However, a functional role for the different sgp130 forms has not been described to date. Here we demonstrate that the metalloproteases ADAM10 and ADAM17 can produce sgp130 by ectodomain shedding of gp130, even though this mechanism only accounts for a minor proportion of sgp130 in the circulation. We further show that full-length sgp130 and the shorter forms sgp130-rheumatoid arthritis-associated peptide (RAPS) and sgp130-E10 are differentially expressed in a cell type- specific manner. Remarkably, full-length sgp130 is expressed by monocytes, but this expression is completely lost during differentiation into macrophages in vitro Using genetically engineered murine pre-B cells that secrete different forms of sgp130, we found that these secreted sgp130 proteins are able to prevent trans-signaling-driven cell proliferation of the secreting cells, whereas conditioned supernatant from these cells failed to block IL-6 trans-signaling in other cells. Thus, our data suggest that the different sgp130 forms are released from cells into their immediate surroundings and appear to form cell-associated gradients to modulate their own susceptibility for IL-6 trans-signaling.
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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.