Nrf2 activation in myeloid cells and endothelial cells differentially mitigates sickle cell disease pathology in mice.
Anemia, Sickle Cell
/ genetics
Animals
Endothelial Cells
/ metabolism
Female
Granulocytes
/ metabolism
Interleukin-1beta
/ genetics
Male
Mice
Mice, Mutant Strains
Monocytes
/ metabolism
NF-E2-Related Factor 2
/ genetics
P-Selectin
/ genetics
Tumor Necrosis Factor-alpha
/ genetics
Vascular Cell Adhesion Molecule-1
/ genetics
Journal
Blood advances
ISSN: 2473-9537
Titre abrégé: Blood Adv
Pays: United States
ID NLM: 101698425
Informations de publication
Date de publication:
23 04 2019
23 04 2019
Historique:
received:
18
02
2018
accepted:
11
03
2019
entrez:
25
4
2019
pubmed:
25
4
2019
medline:
15
5
2020
Statut:
ppublish
Résumé
Sickle cell disease (SCD) is caused by a monogenic mutation of the β-globin gene and affects millions of people worldwide. SCD is associated with sustained hemolytic anemia, vasoocclusion, ischemia-reperfusion injury, oxidative tissue damage, inflammatory cell activation, and systemic endothelial dysfunction. The transcription factor Nrf2 coordinates the expression of a wide variety of genes encoding antioxidant, detoxification, and metabolic enzymes. Nrf2 participates in suppressing proinflammatory cytokines and organ protection in SCD. However, little is known regarding the mechanisms by which Nrf2 ameliorates SCD pathology or how some cells respond to Nrf2 stimuli to alleviate SCD pathology. Here, we asked whether monocytes/granulocytes and/or endothelial cells are particularly critical in alleviating the pathology of SCD. By targeting these cells with a Cre recombinase system, we generated SCD::Keap1F/F::LysM-Cre and Tie1-Cre mice with constitutive Nrf2 activation in monocytes/granulocytes and endothelial cells, respectively. Analyses of SCD::Keap1F/F::LysM-Cre and SCD::Keap1F/F::Tie1-Cre mice revealed significantly reduced inflammation, along with decreased white blood cell counts and lower
Identifiants
pubmed: 31015205
pii: bloodadvances.2018017574
doi: 10.1182/bloodadvances.2018017574
pmc: PMC6482351
doi:
Substances chimiques
IL1B protein, mouse
0
Interleukin-1beta
0
NF-E2-Related Factor 2
0
Nfe2l2 protein, mouse
0
P-Selectin
0
Tumor Necrosis Factor-alpha
0
Vascular Cell Adhesion Molecule-1
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1285-1297Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2019 by The American Society of Hematology.
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