Sustained Immunoparalysis in Endotoxin-Tolerized Monocytic Cells.
Adenosine Triphosphate
/ metabolism
Cell Line
Cells, Cultured
Endotoxins
/ pharmacology
Enzyme-Linked Immunosorbent Assay
Healthy Volunteers
Humans
Lactic Acid
/ metabolism
Leukocytes, Mononuclear
/ drug effects
Lipopolysaccharides
/ pharmacology
NAD
/ metabolism
Real-Time Polymerase Chain Reaction
THP-1 Cells
Journal
Mediators of inflammation
ISSN: 1466-1861
Titre abrégé: Mediators Inflamm
Pays: United States
ID NLM: 9209001
Informations de publication
Date de publication:
2020
2020
Historique:
received:
11
02
2020
revised:
05
05
2020
accepted:
11
05
2020
entrez:
4
7
2020
pubmed:
4
7
2020
medline:
8
6
2021
Statut:
epublish
Résumé
Sepsis is associated with a strong inflammatory reaction triggering a complex and prolonged immune response. Septic patients have been shown to develop sustained immunosuppression due to a reduced responsiveness of leukocytes to pathogens. Changes in cellular metabolism of leukocytes have been linked to this phenomenon and contribute to the ongoing immunological derangement. However, the underlying mechanisms of these phenomena are incompletely understood. In cell culture models, we mimicked LPS tolerance conditions to provide evidence that epigenetic modifications account for monocyte metabolic changes which cause immune paralysis in restimulated septic monocytes. In detail, we observed differential methylation of CpG sites related to metabolic activity in human PBMCs 18 h after septic challenge. The examination of changes in immune function and metabolic pathways was performed in LPS-tolerized monocytic THP-1 cells. Passaged THP-1 cells, inheriting initial LPS challenge, presented with dysregulation of cytokine expression and oxygen consumption for up to 7 days after the initial LPS treatment. Proinflammatory cytokine concentrations of TNF
Identifiants
pubmed: 32617075
doi: 10.1155/2020/8294342
pmc: PMC7306843
doi:
Substances chimiques
Endotoxins
0
Lipopolysaccharides
0
NAD
0U46U6E8UK
Lactic Acid
33X04XA5AT
Adenosine Triphosphate
8L70Q75FXE
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
8294342Informations de copyright
Copyright © 2020 Christina K. Weisheit et al.
Déclaration de conflit d'intérêts
None is declared.
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