{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1363670320164540032.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.4049/jimmunol.1501017"}},{"identifier":{"@type":"URI","@value":"https://academic.oup.com/jimmunol/article-pdf/195/8/3866/62250844/1501017.pdf"}}],"dc:title":[{"@value":"Endotoxemia Induces IκBβ/NF-κB–Dependent Endothelin-1 Expression in Hepatic Macrophages"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:title>Abstract</jats:title>\n               <jats:p>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.</jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1383670320164540037","@type":"Researcher","foaf:name":[{"@value":"Alejandro Bugarini"}],"jpcoar:affiliationName":[{"@value":"Section of Neonatology, Department of Pediatrics, Children’s Hospital Colorado, University of Colorado School of Medicine , Aurora, CO 80045"}]},{"@id":"https://cir.nii.ac.jp/crid/1380866923181995778","@type":"Researcher","foaf:name":[{"@value":"Aimee L Anderson"}],"jpcoar:affiliationName":[{"@value":"Hepatology and Nutrition, Digestive Health Institute, Section of Gastroenterology, Department of Pediatrics, Children’s Hospital Colorado, University of Colorado School of Medicine , Aurora, CO 80045"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670320164539905","@type":"Researcher","foaf:name":[{"@value":"Natarajan Balasubramaniyan"}],"jpcoar:affiliationName":[{"@value":"Hepatology and Nutrition, Digestive Health Institute, Section of Gastroenterology, Department of Pediatrics, Children’s Hospital Colorado, University of Colorado School of Medicine , Aurora, CO 80045"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670320164540034","@type":"Researcher","foaf:name":[{"@value":"Sarah McKenna"}],"jpcoar:affiliationName":[{"@value":"Section of Neonatology, Department of Pediatrics, Children’s Hospital Colorado, University of Colorado School of Medicine , Aurora, CO 80045"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670320164540036","@type":"Researcher","foaf:name":[{"@value":"Megan Gossling"}],"jpcoar:affiliationName":[{"@value":"Section of Neonatology, Department of Pediatrics, Children’s Hospital Colorado, University of Colorado School of Medicine , Aurora, CO 80045"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670320164540032","@type":"Researcher","foaf:name":[{"@value":"Elizabeth Hill"}],"jpcoar:affiliationName":[{"@value":"Section of Neonatology, Department of Pediatrics, Children’s Hospital Colorado, University of Colorado School of Medicine , Aurora, CO 80045"}]},{"@id":"https://cir.nii.ac.jp/crid/1380866923181995779","@type":"Researcher","foaf:name":[{"@value":"Raymond C Rancourt"}],"jpcoar:affiliationName":[{"@value":"Pediatric Airway Research Center, Section of Pulmonology, Department of Pediatrics, University of Colorado School of Medicine , Aurora, CO 80045"}]},{"@id":"https://cir.nii.ac.jp/crid/1380866923181995776","@type":"Researcher","foaf:name":[{"@value":"Clyde J Wright"}],"jpcoar:affiliationName":[{"@value":"Section of Neonatology, Department of Pediatrics, Children’s Hospital Colorado, University of Colorado School of Medicine , Aurora, CO 80045"}]},{"@id":"https://cir.nii.ac.jp/crid/1380866923181995777","@type":"Researcher","foaf:name":[{"@value":"Karim C El Kasmi"}],"jpcoar:affiliationName":[{"@value":"Hepatology and Nutrition, Digestive Health Institute, Section of Gastroenterology, Department of Pediatrics, Children’s Hospital Colorado, University of Colorado School of Medicine , Aurora, CO 80045"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"00221767"},{"@type":"EISSN","@value":"15506606"}],"prism:publicationName":[{"@value":"The Journal of Immunology"}],"dc:publisher":[{"@value":"Oxford University Press (OUP)"}],"prism:publicationDate":"2015-10","prism:volume":"195","prism:number":"8","prism:startingPage":"3866","prism:endingPage":"3879"},"reviewed":"false","dc:rights":["https://academic.oup.com/pages/standard-publication-reuse-rights"],"url":[{"@id":"https://academic.oup.com/jimmunol/article-pdf/195/8/3866/62250844/1501017.pdf"}],"createdAt":"2015-09-05","modifiedAt":"2025-03-07","relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1360285710444811520","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Lipopolysaccharide promotes the development of murine endometriosis‐like lesions via the nuclear factor‐kappa B pathway"}]},{"@id":"https://cir.nii.ac.jp/crid/1360567183435297152","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"T cells upon activation promote endothelin 1 production in monocytes via IFN-γ and TNF-α"}]},{"@id":"https://cir.nii.ac.jp/crid/1360588380149503232","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"<scp>NF</scp>\n                    κ\n                    <scp>B</scp>\n                    dynamics‐dependent epigenetic changes modulate inflammatory gene expression and induce cellular senescence"}]}],"dataSourceIdentifier":[{"@type":"CROSSREF","@value":"10.4049/jimmunol.1501017"},{"@type":"CROSSREF","@value":"10.1111/aji.12631_references_DOI_9Q2DZ1mP8Ynf9eyUGR3mDlTr9xc"},{"@type":"CROSSREF","@value":"10.1038/s41598-017-14202-5_references_DOI_9Q2DZ1mP8Ynf9eyUGR3mDlTr9xc"},{"@type":"CROSSREF","@value":"10.1111/febs.17227_references_DOI_9Q2DZ1mP8Ynf9eyUGR3mDlTr9xc"}]}