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Nicotinamide mononucleotide administration triggers macrophages reprogramming and alleviates inflammation during sepsis induced by experimental peritonitis

ABSTRACT: Peritonitis and subsequent sepsis lead to high morbidity and mortality in response to uncontrolled systemic inflammation primarily mediated by macrophages. We investigated whether the administration of a natural biosynthetic precursor of NAD+, β-nicotinamide mononucleotide (β‐NMN), could prevent clinical deterioration effects of sepsis. To this purpose, C57BL6 mice were subjected to the cecal ligation and puncture (CLP) model to provoke sepsis or were injected with thioglycolate (TGC) to induce a sterile peritonitis with recruitment and differentiation of macrophages into the inflamed peritoneal cavity. β-NMN was administered for 4 days after CLP and for 3 days post TGC treatment. Administration of β‐NMN decreased bacterial load in blood and reduced clinical signs of distress and mortality during sepsis. Transcriptomic analysis of hearts and lungs 24 hours post CLP-induction, revealed that β-NMN downregulated genes controlling immuno-inflammatory response and upregulated genes involved in bioenergetic metabolism, mitochondria biogenesis, and autophagy. In the thioglycolate model, β‐NMN treatment significantly reduced phagolysosomes acidification and inflammatory mediators secretion from bacteria-stimulated peritoneal macrophages. Transcriptomic signature of these macrophages showed that β‐NMN administration limited the pro-inflammatory M1 phenotype, induced the expression of specific markers of M2 type macrophages and significantly impacted gens involved in NAD+ metabolism.

ORGANISM(S): Mus musculus

PROVIDER: GSE199156 | GEO | 2022/06/08

REPOSITORIES: GEO

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Long-term administration of nicotinamide mononucleotide mitigates age-associated physiological decline in mice

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2016-12-01 | GSE85718 | GEO

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2022-02-22 | PXD027471 | Pride

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2017-07-21 | PXD006754 | Pride

Profiling circulating microRNA expression in experimental sepsis by cecal ligation and puncture

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2015-05-15 | E-GEOD-47094 | biostudies-arrayexpress

Nicotinamide mononucleotide administration triggers macrophages reprogramming and alleviates inflammation during sepsis induced by experimental peritonitis

Project description:Nicotinamide mononucleotide administration triggers macrophages reprogramming and alleviates inflammation during sepsis induced by experimental peritonitis

| PRJNA818667 | ENA

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