ArticleScientific reports2017
Meprin Metalloproteases Generate Biologically Active Soluble Interleukin-6 Receptor to Induce Trans-Signaling.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 56 citations in OpenAlex.
- Serum meprin α levels for the detection of systemic inflammatory response syndrome.Molecular medicine (Cambridge, Mass.) · 2026Article
- Meprin proteases in cutaneous homeostasis and psoriasis: pathophysiological mechanisms and therapeutic prospects.Frontiers in immunology · 2026Review
- Type I interferon limits interleukin-6 signalling in SLE through shedding interleukin-6 receptors.Rheumatology (Oxford, England) · 2025Article
- Targeted approach to determine the impact of cancer-associated protease variants.Science advances · 2025Article
- The role of DPYD and the effects of DPYD suppressor luteolin combined with 5-FU in pancreatic cancer.Cancer medicine · 2024Article
- Targeting IL-6 trans-signalling: past, present and future prospects.Nature reviews. Immunology · 2023Review
- The putative pleiotropic functions of meprin β in gastric cancer.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2023Article
- ADAM10-a "multitasker" in sepsis: focus on its posttranslational target.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023Review
- Proteolysis of CD44 at the cell surface controls a downstream protease network.Frontiers in molecular biosciences · 2023Article
- A zebrafish HCT116 xenograft model to predict anandamide outcomes on colorectal cancer.Cell death & disease · 2022Article
- Therapeutic potential of human serum albumin nanoparticles encapsulated actinonin in murine model of lung adenocarcinoma.Drug delivery · 2022Article
- Helical ultrastructure of the metalloprotease meprin α in complex with a small molecule inhibitor.Nature communications · 2022Article
- Meprin β expression modulates the interleukin-6 mediated JAK2-STAT3 signaling pathway in ischemia/reperfusion-induced kidney injury.Physiological reports · 2022Article
- Structural and evolutionary insights into astacin metallopeptidases.Frontiers in molecular biosciences · 2022Article
- A preliminary study of possible fibrotic role of meprin metalloproteases in scleroderma patients.Archives of rheumatology · 2021Article
- Distinct contributions of meprins to skin regeneration after injury - Meprin α a physiological processer of pro-collagen VII.Matrix biology plus · 2021Article
- Characterization of the Cancer-Associated Meprin Βeta Variants G45R and G89R.Frontiers in molecular biosciences · 2021Article
- Cathepsin S provokes interleukin-6 (IL-6) trans-signaling through cleavage of the IL-6 receptor in vitro.Scientific reports · 2020Article
- Article
- Degradome of soluble ADAM10 and ADAM17 metalloproteases.Cellular and molecular life sciences : CMLS · 2020Article
Corrections and comments
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Authors and funding
17 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Soluble Interleukin-6 receptor (sIL-6R) mediated trans-signaling is an important pro-inflammatory stimulus associated with pathological conditions, such as arthritis, neurodegeneration and inflammatory bowel disease. The sIL-6R is generated proteolytically from its membrane bound form and A Disintegrin And Metalloprotease (ADAM) 10 and 17 were shown to perform ectodomain shedding of the receptor in vitro and in vivo. However, under certain conditions not all sIL-6R could be assigned to ADAM10/17 activity. Here, we demonstrate that the IL-6R is a shedding substrate of soluble meprin α and membrane bound meprin β, resulting in bioactive sIL-6R that is capable of inducing IL-6 trans-signaling. We determined cleavage within the N-terminal part of the IL-6R stalk region, distinct from the cleavage site reported for ADAM10/17. Interestingly, meprin β can be shed from the cell surface by ADAM10/17 and the observation that soluble meprin β is not capable of shedding the IL-6R suggests a regulatory mechanism towards trans-signaling. Additionally, we observed a significant negative correlation of meprin β expression and IL-6R levels on human granulocytes, providing evidence for in vivo function of this proteolytic interaction.
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