{"@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/1362825893283714816.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1073/pnas.202296999"}},{"identifier":{"@type":"URI","@value":"https://pnas.org/doi/pdf/10.1073/pnas.202296999"}}],"dc:title":[{"@value":"Lipoxin A<sub>4</sub>and aspirin-triggered 15-epi-lipoxin A<sub>4</sub>inhibit peroxynitrite formation, NF-κB and AP-1 activation, and IL-8 gene expression in human leukocytes"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:p>Lipoxin A<jats:sub>4</jats:sub>(LXA<jats:sub>4</jats:sub>) and aspirin-triggered 15-epi-LXA<jats:sub>4</jats:sub>(ATL) are emerging as endogenous braking signals for neutrophil-mediated tissue injury. Recent studies indicate that peroxynitrite (ONOO<jats:sup>−</jats:sup>) may function as an intracellular signal for the production of IL-8, a potent proinflammatory cytokine in human leukocytes. In this study, we evaluated the impact of the metabolically stable analogues of LXA<jats:sub>4</jats:sub>/ATL on lipopolysaccharide (LPS)-induced ONOO<jats:sup>−</jats:sup>formation and ONOO<jats:sup>−</jats:sup>-mediated IL-8 gene expression in human leukocytes. At nanomolar concentrations, LXA<jats:sub>4</jats:sub>analogues markedly reduced LPS-stimulated superoxide formation, evoked increases in intracellular diamino-fluorescein fluorescence (an indicator of NO formation), and consequently reduced ONOO<jats:sup>−</jats:sup>formation in isolated neutrophils, as well as in neutrophils, monocytes, and lymphocytes, in whole blood. LXA<jats:sub>4</jats:sub>/ATL analogues attenuated nuclear accumulation of activator protein-1 and nuclear factor-κB in both polymorphonuclear and mononuclear leukocytes and inhibited IL-8 mRNA expression and IL-8 release by 50–65% in response to LPS. The LXA<jats:sub>4</jats:sub>inhibitory responses were concentration dependent and were not shared by 15-deoxy-LXA<jats:sub>4</jats:sub>. None of the LXA<jats:sub>4</jats:sub>analogues studied affected neutrophil survival, nor reversed the apoptosis delaying action of LPS in neutrophils. In addition, LXA<jats:sub>4</jats:sub>analogues had no significant effect on exogenous ONOO<jats:sup>−</jats:sup>-induced IL-8 gene and protein expression. These findings suggest that by attenuating ONOO<jats:sup>−</jats:sup>formation, LXA<jats:sub>4</jats:sub>and ATL can oppose ONOO<jats:sup>−</jats:sup>signaling in leukocytes and provide a rationale for using stable synthetic analogues as antiinflammatory compounds<jats:italic>in vivo</jats:italic>.</jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1380294662793991680","@type":"Researcher","foaf:name":[{"@value":"Levente József"}],"jpcoar:affiliationName":[{"@value":"Research Center, Maisonneuve-Rosemont Hospital and Department of Medicine, University of Montréal, Montréal, QC, Canada H1T 2M4; Department of Chemistry, University of Southern California, Los Angeles, CA 90089; and Center for Experimental Therapeutics and Reperfusion Injury, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115"}]},{"@id":"https://cir.nii.ac.jp/crid/1380294662793991683","@type":"Researcher","foaf:name":[{"@value":"Christine Zouki"}],"jpcoar:affiliationName":[{"@value":"Research Center, Maisonneuve-Rosemont Hospital and Department of Medicine, University of Montréal, Montréal, QC, Canada H1T 2M4; Department of Chemistry, University of Southern California, Los Angeles, CA 90089; and Center for Experimental Therapeutics and Reperfusion Injury, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115"}]},{"@id":"https://cir.nii.ac.jp/crid/1380294662793991684","@type":"Researcher","foaf:name":[{"@value":"Nicos A. Petasis"}],"jpcoar:affiliationName":[{"@value":"Research Center, Maisonneuve-Rosemont Hospital and Department of Medicine, University of Montréal, Montréal, QC, Canada H1T 2M4; Department of Chemistry, University of Southern California, Los Angeles, CA 90089; and Center for Experimental Therapeutics and Reperfusion Injury, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115"}]},{"@id":"https://cir.nii.ac.jp/crid/1380294662793991681","@type":"Researcher","foaf:name":[{"@value":"Charles N. Serhan"}],"jpcoar:affiliationName":[{"@value":"Research Center, Maisonneuve-Rosemont Hospital and Department of Medicine, University of Montréal, Montréal, QC, Canada H1T 2M4; Department of Chemistry, University of Southern California, Los Angeles, CA 90089; and Center for Experimental Therapeutics and Reperfusion Injury, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115"}]},{"@id":"https://cir.nii.ac.jp/crid/1380294662793991682","@type":"Researcher","foaf:name":[{"@value":"János G. Filep"}],"jpcoar:affiliationName":[{"@value":"Research Center, Maisonneuve-Rosemont Hospital and Department of Medicine, University of Montréal, Montréal, QC, Canada H1T 2M4; Department of Chemistry, University of Southern California, Los Angeles, CA 90089; and Center for Experimental Therapeutics and Reperfusion Injury, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"00278424"},{"@type":"EISSN","@value":"10916490"}],"prism:publicationName":[{"@value":"Proceedings of the National Academy of Sciences"}],"dc:publisher":[{"@value":"Proceedings of the National Academy of Sciences"}],"prism:publicationDate":"2002-09-16","prism:volume":"99","prism:number":"20","prism:startingPage":"13266","prism:endingPage":"13271"},"reviewed":"false","url":[{"@id":"https://pnas.org/doi/pdf/10.1073/pnas.202296999"}],"createdAt":"2002-10-01","modifiedAt":"2024-01-07","relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1360017282211432960","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Nitric Oxide Derived from Cytoglobin-Deficient Hepatic Stellate Cells Causes Suppression of Cytochrome\n                    <i>c</i>\n                    Oxidase Activity in Hepatocytes"}]},{"@id":"https://cir.nii.ac.jp/crid/1360283693411939840","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Lipoxin A4 Reduces Lipopolysaccharide-Induced Inflammation in Macrophages and Intestinal Epithelial Cells through Inhibition of Nuclear Factor-κB Activation"}]},{"@id":"https://cir.nii.ac.jp/crid/1360565168304114432","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Regulation of immune responses by neutrophils"}]},{"@id":"https://cir.nii.ac.jp/crid/1390001204633870336","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Chemical Mediators and the Resolution of Airway Inflammation"}]}],"dataSourceIdentifier":[{"@type":"CROSSREF","@value":"10.1073/pnas.202296999"},{"@type":"CROSSREF","@value":"10.1124/jpet.109.159046_references_DOI_AJX84AxigrR9mBEigWq6hKxhtXu"},{"@type":"CROSSREF","@value":"10.1111/nyas.12445_references_DOI_AJX84AxigrR9mBEigWq6hKxhtXu"},{"@type":"CROSSREF","@value":"10.1089/ars.2021.0279_references_DOI_AJX84AxigrR9mBEigWq6hKxhtXu"},{"@type":"CROSSREF","@value":"10.2332/allergolint.08-rai-0018_references_DOI_AJX84AxigrR9mBEigWq6hKxhtXu"}]}