Evidence map›Paper›PMID 35767602›Full record

ArticleScience advances2022

Immunomodulatory actions of a kynurenine-derived endogenous electrophile.

Mara Carreño, Maria F Pires, Steven R Woodcock, Tomasz Brzoska, Samit Ghosh, Sonia R Salvatore, Fei Chang, Nicholas K H Khoo, Matthew Dunn, Nora Connors and 9 more

Open access · goldAbstract read
In one paragraph

Article in Science advances, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.2field-weighted citation impact, top 22% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed, 18 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Metabolic adaptations rewire CD4Nature immunology · 2026
    Article
  5. Review
  6. Article
  7. Review
  8. Article
  9. The chemical biology of dinitrogen trioxide.Redox biochemistry and chemistry · 2024
    Article
  10. Review
  11. Extracellular Vesicle Size Reveals Cargo Specific to Coagulation and Inflammation in Pediatric and Adult Sickle Cell Disease.Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis
    Observational
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors at 3 institutions in 2 countries.

Mara CarreñoDepartment of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, USA.ORCID 0000-0002-7246-4248
Maria F PiresDepartment of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, USA.ORCID 0000-0001-9343-856X
Steven R WoodcockDepartment of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, USA.ORCID 0000-0002-4075-1883
Tomasz BrzoskaPittsburgh Heart, Lung and Blood Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA, USA.ORCID 0000-0002-7431-3590
Samit GhoshPittsburgh Heart, Lung and Blood Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA, USA.
Sonia R SalvatoreDepartment of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, USA.ORCID 0000-0002-9942-3905
Fei ChangDepartment of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, USA.ORCID 0000-0002-3724-2455
Nicholas K H KhooDepartment of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, USA.
Matthew DunnDepartment of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, USA.
Nora ConnorsDepartment of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, USA.ORCID 0000-0002-9461-0701
Shuai YuanPittsburgh Heart, Lung and Blood Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA, USA.ORCID 0000-0002-9590-6555
Adam C StraubDepartment of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, USA.
Stacy G WendellDepartment of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, USA.ORCID 0000-0001-9083-6933
Gregory J KatoCSL Behring, King of Prussia, PA, USA.ORCID 0000-0003-4465-3217
Bruce A FreemanDepartment of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, USA.ORCID 0000-0002-2028-8369
Solomon F Ofori-AcquahPittsburgh Heart, Lung and Blood Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA, USA.
Prithu SunddPittsburgh Heart, Lung and Blood Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA, USA.ORCID 0000-0001-7568-5719
Francisco J SchopferDepartment of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, USA.ORCID 0000-0001-9526-695X
Dario A VitturiDepartment of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, USA.ORCID 0000-0003-0354-4567
University of Pittsburgh · USCSL (United States) · USUniversity of Ghana · GH

Funding

Vascular Subphenotypes of Lung DiseaseP01HL103455 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI MORRIS, ALISON · 2011 to 2020
$26.1M
Single Nephron and MetabolomicsP30DK079307 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI KLEYMAN, THOMAS R · 2008 to 2022
$13.4M
Pittsburgh Liver Research CenterP30DK120531 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI DAVID A GELLER · 2019 to 2026
$10.9M
Redox-Derived Pulmonary Anti-Inflammatory MediatorsR01HL064937 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI FREEMAN, BRUCE ALAN · 2000 to 2015
$5.6M
SickleGenAfrica:Sickle Cell Disease Genomics Network of AfricaU54HL141011 · NHLBI · UNIVERSITY OF GHANA · PI OFORI-ACQUAH, SOLOMON FIIFI · 2017 to 2021
$5.5M
Pulmonary arteriole occlusion by platelet-neutrophil micro-emboli in Acute Chest SyndromeR01HL128297 · NHLBI · VERSITI WISCONSIN, INC. · PI SUNDD, PRITHU · 2015 to 2025
$5.4M
Basic and Translational Studies in Redox Regulation of Cardiovascular Physiology and DiseaseR35HL161177 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Adam Carl Straub · 2022 to 2026
$4.7M
Formation and metabolism of nitrated fatty acidsR01GM125944 · NIGMS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI SCHOPFER, FRANCISCO JOSE · 2018 to 2025
$3.4M
NITRIC OXIDE REGULATION OF VASCULAR OXIDANT INJURYR01HL058115 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI FREEMAN, BRUCE ALAN · 1998 to 2007
$3.3M
Mechanisms of platelet exosome-mediated acute chest syndrome in sickle cell diseaseR01HL141080 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI NEAL, MATTHEW D, NOVELLI, ENRICO M · 2019 to 2022
$3.1M
Renal endothelium and the development of chronic kidney disease in sickle cell disordersR01DK132145 · NIDDK · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Samit Ghosh · 2023 to 2026
$2.5M
Novel role of smooth muscle B5 reductase in Sickle Cell DiseaseR01HL133864 · NHLBI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI STRAUB, ADAM CARL · 2016 to 2019
$2.4M
NHLBI NIH HHS K01 HL133331NHLBI NIH HHS P01 HL103455NHLBI NIH HHS R01 HL058115NHLBI NIH HHS R01 HL064937NHLBI NIH HHS R01 HL128297NHLBI NIH HHS R01 HL128304NHLBI NIH HHS R01 HL133864NHLBI NIH HHS R01 HL141080NHLBI NIH HHS R03 HL157878NHLBI NIH HHS R35 HL161177NHLBI NIH HHS U54 HL141011NIAID NIH HHS R56 AI165479NIDDK NIH HHS P30 DK079307NIDDK NIH HHS P30 DK120531NIDDK NIH HHS R01 DK112854NIDDK NIH HHS R01 DK124426NIDDK NIH HHS R01 DK124510NIDDK NIH HHS R01 DK132145NIGMS NIH HHS R01 GM125944
6 · The paper itself

Abstract

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.

Identifiers

PMID35767602
PMCPMC9242454
OpenAlexW4283725452

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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.