ArticleJournal of immunology (Baltimore, Md. : 1950)2015
Endotoxemia Induces IκBβ/NF-κB-Dependent Endothelin-1 Expression in Hepatic Macrophages.
Article in Journal of immunology (Baltimore, Md. : 1950), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
24 citing papers in PubMed, 41 citations in OpenAlex.
- Endothelin-1 signaling in the kidney: recent advances and remaining gaps.American journal of physiology. Renal physiology · 2025Review
- Implications of neonatal absence of innate immune mediated NFκB/AP1 signaling in the murine liver.Pediatric research · 2024Article
- Aspirin Caused Intestinal Damage through FXR and ET-1 Signaling Pathways.International journal of molecular sciences · 2024Article
- Endothelin-1 in Health and Disease.International journal of molecular sciences · 2023Review
- The Role of Plasminogen Activator Inhibitor 1 in Predicting Sepsis-Associated Liver Dysfunction: An Observational Study.International journal of environmental research and public health · 2023Observational
- Endothelin receptor antagonism improves glucose tolerance and adipose tissue inflammation in an experimental model of systemic lupus erythematosus.American journal of physiology. Endocrinology and metabolism · 2023Article
- APAP-Induced IκBβ/NFκB Signaling Drives Hepatic Il6 Expression and Associated Sinusoidal Dilation.Toxicological sciences : an official journal of the Society of Toxicology · 2022Article
- The Acute Hepatic NF-κB-Mediated Proinflammatory Response to Endotoxemia Is Attenuated in Intrauterine Growth-Restricted Newborn Mice.Frontiers in immunology · 2021Article
- Loss of Hepatic Carcinoembryonic Antigen-Related Cell Adhesion Molecule 1 Links Nonalcoholic Steatohepatitis to Atherosclerosis.Hepatology communications · 2020Article
- Article
- CpG-ODN-mediated TLR9 innate immune signalling and calcium dyshomeostasis converge on the NFκB inhibitory protein IκBβ to drive IL1α and IL1β expression.Immunology · 2020Article
- An Hb-mediated circulating macrophage contributing to pulmonary vascular remodeling in sickle cell disease.JCI insight · 2019Article
- Short Bowel Syndrome as the Leading Cause of Intestinal Failure in Early Life: Some Insights into the Management.Pediatric gastroenterology, hepatology & nutrition · 2019Review
- Developmentally Regulated Innate Immune NFκB Signaling Mediates IL-1α Expression in the Perinatal Murine Lung.Frontiers in immunology · 2019Article
- Gene Expression of Protein Tyrosine Phosphatase 1B and Endoplasmic Reticulum Stress During Septic Shock.Frontiers in medicine · 2019Article
- Immunotolerant p50/NFκB Signaling and Attenuated Hepatic IFNβ Expression Increases Neonatal Sensitivity to Endotoxemia.Frontiers in immunology · 2018Article
- Inhibition of IκBβ/NFκB signaling prevents LPS-induced IL1β expression without increasing apoptosis in the developing mouse lung.Pediatric research · 2017Article
- T cells upon activation promote endothelin 1 production in monocytes via IFN-γ and TNF-α.Scientific reports · 2017Article
- Roflumilast reverses polymicrobial sepsis-induced liver damage by inhibiting inflammation in mice.Laboratory investigation; a journal of technical methods and pathology · 2017Article
- Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Elevated serum concentrations of the vasoactive protein endothelin-1 (ET-1) occur in the setting of systemic inflammatory response syndrome and contribute to distal organ hypoperfusion and pulmonary hypertension. Thus, understanding the cellular source and transcriptional regulation of systemic inflammatory stress-induced ET-1 expression may reveal therapeutic targets. Using a murine model of LPS-induced septic shock, we demonstrate that the hepatic macrophage is the primary source of elevated circulating ET-1, rather than the endothelium as previously proposed. Using pharmacologic inhibitors, ET-1 promoter luciferase assays, and by silencing and overexpressing NF-κB inhibitory protein IκB expression, we demonstrate that LPS-induced ET-1 expression occurs via an NF-κB-dependent pathway. Finally, the specific role of the cRel/p65 inhibitory protein IκBβ was evaluated. Although cytoplasmic IκBβ inhibits activity of cRel-containing NF-κB dimers, nuclear IκBβ stabilizes NF-κB/DNA binding and enhances gene expression. Using targeted pharmacologic therapies to specifically prevent IκBβ/NF-κB signaling, as well as mice genetically modified to overexpress IκBβ, we show that nuclear IκBβ is both necessary and sufficient to drive LPS-induced ET-1 expression. Together, these results mechanistically link the innate immune response mediated by IκBβ/NF-κB to ET-1 expression and potentially reveal therapeutic targets for patients with Gram-negative septic shock.
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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.