دورية أكاديمية
أعرض في EDS

Immunomodulatory actions of a kynurenine-derived endogenous electrophile.

التفاصيل البيبلوغرافية
العنوان: Immunomodulatory actions of a kynurenine-derived endogenous electrophile.
المؤلفون: Carreño M; Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, USA., Pires MF; Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, USA., Woodcock SR; Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, USA., Brzoska T; Pittsburgh Heart, Lung and Blood Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA, USA.; Division of Hematology/Oncology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA., Ghosh S; Pittsburgh Heart, Lung and Blood Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA, USA.; Division of Hematology/Oncology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA., Salvatore SR; Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, USA., Chang F; Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, USA., Khoo NKH; Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, USA.; Pittsburgh Liver Research Center, University of Pittsburgh, Pittsburgh, PA, USA., Dunn M; Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, USA., Connors N; Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, USA., Yuan S; Pittsburgh Heart, Lung and Blood Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA, USA., Straub AC; Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, USA.; Pittsburgh Heart, Lung and Blood Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA, USA.; Center for Microvascular Research, University of Pittsburgh, Pittsburgh, PA, USA., Wendell SG; Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, USA.; Pittsburgh Liver Research Center, University of Pittsburgh, Pittsburgh, PA, USA., Kato GJ; CSL Behring, King of Prussia, PA, USA., Freeman BA; Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, USA., Ofori-Acquah SF; Pittsburgh Heart, Lung and Blood Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA, USA.; Division of Hematology/Oncology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.; School of Biomedical and Allied Health Sciences, University of Ghana, Accra, Ghana., Sundd P; Pittsburgh Heart, Lung and Blood Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA, USA.; Division of Hematology/Oncology, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.; Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA., Schopfer FJ; Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, USA.; Pittsburgh Heart, Lung and Blood Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA, USA.; Pittsburgh Liver Research Center, University of Pittsburgh, Pittsburgh, PA, USA., Vitturi DA; Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, USA.; Pittsburgh Heart, Lung and Blood Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA, USA.; Center for Critical Care Nephrology, University of Pittsburgh, Pittsburgh, PA, USA.
المصدر: Science advances [Sci Adv] 2022 Jul; Vol. 8 (26), pp. eabm9138. Date of Electronic Publication: 2022 Jun 29.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: American Association for the Advancement of Science Country of Publication: United States NLM ID: 101653440 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2375-2548 (Electronic) Linking ISSN: 23752548 NLM ISO Abbreviation: Sci Adv Subsets: PubMed not MEDLINE; MEDLINE
أسماء مطبوعة: Original Publication: Washington, DC : American Association for the Advancement of Science, [2015]-
مستخلص: The up-regulation of kynurenine metabolism induces immunomodulatory responses via incompletely understood mechanisms. We report that increases in cellular and systemic kynurenine levels yield the electrophilic derivative kynurenine-carboxyketoalkene (Kyn-CKA), as evidenced by the accumulation of thiol conjugates and saturated metabolites. Kyn-CKA induces NFE2 like bZIP transcription factor 2- and aryl hydrocarbon receptor-regulated genes and inhibits nuclear factor κB- and NLR family pyrin domain containing 3-dependent proinflammatory signaling. Sickle cell disease (SCD) is a hereditary hemolytic condition characterized by basal inflammation and recurrent vaso-occlusive crises. Both transgenic SCD mice and patients with SCD exhibit increased kynurenine and Kyn-CKA metabolite levels. Plasma hemin and kynurenine concentrations are positively correlated, indicating that Kyn-CKA synthesis in SCD is up-regulated during pathogenic vascular stress. Administration of Kyn-CKA abrogated pulmonary microvasculature occlusion in SCD mice, an important factor in lung injury development. These findings demonstrate that the up-regulation of kynurenine synthesis and its metabolism to Kyn-CKA is an adaptive response that attenuates inflammation and protects tissues.
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معلومات مُعتمدة: R01 DK112854 United States DK NIDDK NIH HHS; R01 HL133864 United States HL NHLBI NIH HHS; R01 DK124426 United States DK NIDDK NIH HHS; K01 HL133331 United States HL NHLBI NIH HHS; R01 HL128297 United States HL NHLBI NIH HHS; P30 DK120531 United States DK NIDDK NIH HHS; R35 HL161177 United States HL NHLBI NIH HHS; R01 HL128304 United States HL NHLBI NIH HHS; U54 HL141011 United States HL NHLBI NIH HHS; R01 HL141080 United States HL NHLBI NIH HHS; R56 AI165479 United States AI NIAID NIH HHS; R01 GM125944 United States GM NIGMS NIH HHS; P30 DK079307 United States DK NIDDK NIH HHS; P01 HL103455 United States HL NHLBI NIH HHS; R01 HL058115 United States HL NHLBI NIH HHS; R01 DK124510 United States DK NIDDK NIH HHS; R01 HL064937 United States HL NHLBI NIH HHS; R03 HL157878 United States HL NHLBI NIH HHS
تواريخ الأحداث: Date Created: 20220629 Latest Revision: 20240923
رمز التحديث: 20240923
مُعرف محوري في PubMed: PMC9242454
DOI: 10.1126/sciadv.abm9138
PMID: 35767602
قاعدة البيانات: MEDLINE
الوصف
تدمد:2375-2548
DOI:10.1126/sciadv.abm9138