ArticleScience signaling2015
Shedding of the tumor necrosis factor (TNF) receptor from the surface of hepatocytes during sepsis limits inflammation through cGMP signaling.
Article in Science signaling, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 64 citations in OpenAlex.
- High cut-off dialysis mitigates pro-calcific effects of plasma on vascular progenitor cells.Scientific reports · 2021Trial
- Diagnostic and Prognostic Biomarkers for Sepsis-Associated Liver Injury: Current Status and Future Perspectives.Gastroenterology research and practice · 2026Review
- Biomarkers trajectories in critically ill patients with COVID-19 acute respiratory distress syndrome: insights from latent class growth analysis.BMC pulmonary medicine · 2025Article
- Regulation of plasma soluble receptors of TNF and IL-1 in patients with COVID-19 differs from that observed in sepsis.The Journal of infection · 2024Article
- Impact ofBiomedicines · 2024Article
- Extracellular SOD modulates canonical TNFα signaling and α5β1 integrin transactivation in vascular smooth muscle cells.Free radical biology & medicine · 2023Article
- Zafirlukast Is a Promising Scaffold for Selectively Inhibiting TNFR1 Signaling.ACS bio & med chem Au · 2023Article
- RIPK3 promoter hypermethylation in hepatocytes protects from bile acid-induced inflammation and necroptosis.Cell death & disease · 2023Article
- ADAM10-a "multitasker" in sepsis: focus on its posttranslational target.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023Review
- Urinary angiotensin-converting enzyme 2 and metabolomics in COVID-19-mediated kidney injury.Clinical kidney journal · 2023Article
- Intraperitoneal injection of class A TLR9 agonist enhances anti-PD-1 immunotherapy in colorectal peritoneal metastases.JCI insight · 2022Article
- Article
- Modulation of Inflammatory Cytokine Production in Human Monocytes by cGMP and IRAK3.International journal of molecular sciences · 2022Article
- Bioinformatics Analysis Identifies TNFRSF1A as a Biomarker of Liver Injury in Sepsis TNFRSF1A is a Biomarker for Septic Liver Injury.Genetics research · 2022Article
- Involvement of shedding induced by ADAM17 on the nitric oxide pathway in hypertension.Frontiers in molecular biosciences · 2022Review
- Soluble TNF receptors predict acute kidney injury and mortality in critically ill COVID-19 patients: A prospective observational study.Cytokine · 2022Observational
- The pseudoprotease iRhom1 controls ectodomain shedding of membrane proteins in the nervous system.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- ADAM10 and ADAM17 regulate EGFR, c-Met and TNF RI signalling in liver regeneration and fibrosis.Scientific reports · 2021Article
- Modulation of the tumor micro-environment by CD8Current opinion in immunology · 2021Review
- Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Proteolytic cleavage of the tumor necrosis factor (TNF) receptor (TNFR) from the cell surface contributes to anti-inflammatory responses and may be beneficial in reducing the excessive inflammation associated with multiple organ failure and mortality during sepsis. Using a clinically relevant mouse model of polymicrobial abdominal sepsis, we found that the production of inducible nitric oxide synthase (iNOS) in hepatocytes led to the cyclic guanosine monophosphate (cGMP)-dependent activation of the protease TACE (TNF-converting enzyme) and the shedding of TNFR. Furthermore, treating mice with a cGMP analog after the induction of sepsis increased TNFR shedding and decreased systemic inflammation. Similarly, increasing the abundance of cGMP with a clinically approved phosphodiesterase 5 inhibitor (sildenafil) also decreased markers of systemic inflammation, protected against organ injury, and increased circulating amounts of TNFR1 in mice with sepsis. We further confirmed that a similar iNOS-cGMP-TACE pathway was required for TNFR1 shedding by human hepatocytes in response to the bacterial product lipopolysaccharide. Our data suggest that increasing the bioavailability of cGMP might be beneficial in ameliorating the inflammation associated with sepsis.
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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.