Upregulation of Cullin1 neddylation promotes glycolysis and M1 polarization of macrophage via NF-κB p65 pathway in sepsis.
Animals
Cullin Proteins
/ metabolism
Sepsis
/ metabolism
Mice
Glycolysis
NEDD8 Protein
/ metabolism
Macrophages
/ metabolism
Transcription Factor RelA
/ metabolism
RAW 264.7 Cells
Humans
Up-Regulation
Signal Transduction
Male
Mice, Inbred C57BL
Cyclopentanes
/ pharmacology
Pyrimidines
/ pharmacology
Inflammation
/ metabolism
Glycolysis
Inflammation
Macrophage polarization
NF-κB p65
Neddylation
Sepsis
Journal
Functional & integrative genomics
ISSN: 1438-7948
Titre abrégé: Funct Integr Genomics
Pays: Germany
ID NLM: 100939343
Informations de publication
Date de publication:
30 Oct 2024
30 Oct 2024
Historique:
received:
04
03
2024
accepted:
20
10
2024
revised:
18
07
2024
medline:
31
10
2024
pubmed:
30
10
2024
entrez:
30
10
2024
Statut:
epublish
Résumé
This study aimed to explore the underlying mechanism of neddylation in macrophage polarization during sepsis. A mouse model of sepsis was established by cecal ligation and puncture (CLP). ELISA and Flow cytometry were performed to analyze the generation of pro-inflammatory factors and M1/M2 macrophage polarization, respectively. Western blotting was applied to detect NEDD8-mediated neddylation and glycolysis-related proteins. ECAR method was used to analyze the glycolysis level. HE staining was applied to detect the lung injury. The bacterial load in peritoneal cavity and peripheral blood was determined by counting the colony-forming units. The results showed the upregulated neddylation, M1 polarization and glycolysis of macrophage in patients with sepsis and CLP-challenged mice. NEDD8-mediated Cullin1 neddylation promoted M1 polarization and glycolysis to accelerate inflammation via NF-κB p65 pathway in E.coli-treated Raw264.7 cells. MLN4924 treatment alleviated sepsis by inhibiting neddylation to prevent M1 polarization in CLP-challenged mice. In summary, this study demonstrated that upregulation of NEDD8-mediated Cullin1 neddylation promotes glycolysis and M1 polarization of macrophage via NF-κB p65 pathway, accelerating inflammation in sepsis.
Identifiants
pubmed: 39476129
doi: 10.1007/s10142-024-01483-z
pii: 10.1007/s10142-024-01483-z
doi:
Substances chimiques
Cullin Proteins
0
NEDD8 Protein
0
Cullin 1
0
Transcription Factor RelA
0
pevonedistat
S3AZD8D215
NEDD8 protein, human
0
Nedd8 protein, mouse
0
Cyclopentanes
0
Pyrimidines
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
204Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
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