Intracellular NAD+ levels are associated with LPS-induced TNF-α release in pro-inflammatory macrophages

Bioscience Reports
Abbas Jawad Al-ShabanyRichard A Billington

Abstract

Metabolism and immune responses have been shown to be closely linked and as our understanding increases, so do the intricacies of the level of linkage. NAD(+) has previously been shown to regulate tumour necrosis factor-α (TNF-α) synthesis and TNF-α has been shown to regulate NAD(+) homoeostasis providing a link between a pro-inflammatory response and redox status. In the present study, we have used THP-1 differentiation into pro- (M1-like) and anti- (M2-like) inflammatory macrophage subset models to investigate this link further. Pro- and anti-inflammatory macrophages showed different resting NAD(+) levels and expression levels of NAD(+) homoeostasis enzymes. Challenge with bacterial lipopolysaccharide, a pro-inflammatory stimulus for macrophages, caused a large, biphasic and transient increase in NAD(+) levels in pro- but not anti-inflammatory macrophages that were correlated with TNF-α release and inhibition of certain NAD(+) synthesis pathways blocked TNF-α release. Lipopolysaccharide stimulation also caused changes in mRNA levels of some NAD(+) homoeostasis enzymes in M1-like cells. Surprisingly, despite M2-like cells not releasing TNF-α or changing NAD(+) levels in response to lipopolysaccharide, they showed similar mRNA ...Continue Reading

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Citations

Oct 18, 2018·International Immunology·Amit Singhal, Catherine Youting Cheng
Apr 17, 2020·PLoS Pathogens·Julia María Coronas-SernaSuzana P Salcedo
May 6, 2019·Innate Immunity·Katharina PetinSunna Hauschildt
Jun 2, 2020·Frontiers in Pharmacology·Ubaldina GalliAmbra A Grolla
Mar 9, 2021·Frontiers in Immunology·Subhadip ChoudhuriNisha Jain Garg

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Methods Mentioned

BETA
PMA
ELISA
PCR
electrophoresis

Software Mentioned

Statgraphics
Soft max Pro

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