Mar 30, 2020

NAD+ prevents septic shock by non-canonical inflammasome blockade and IL-10

BioRxiv : the Preprint Server for Biology
Irene Miriam KaplowAbdallah Elkhal

Abstract

Non-canonical inflammasome activation is crucial in the development of septic shock promoting pyroptosis and pro-inflammatory cytokine production via caspase-11 and Gasdermin-D (GSDMD). Here, we show that NAD+ treatment protected mice towards bacterial and LPS induced endotoxic shock by blocking the non-canonical inflammasome specifically. NAD+ administration impeded systemic IL-1{beta} and IL-18 production and GSDMD-mediated pyroptosis of macrophages via the IFN-{beta}/STAT-1 signaling machinery. More importantly, NAD+ administration not only improved casp-11-/- survival but rendered WT mice completely resistant to septic shock via the IL-10 signaling pathway that was independent from the non-canonical inflammasome. Here, we delineated a two-sided effect of NAD+ blocking septic shock through a specific inhibition of the non canonical inflammasome and promoting immune homeostasis via IL-10, underscoring its unique therapeutic potential.

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Study
Hydrogen sulfite
DNA Methylation [PE]
Protein Methylation
Genome
DNA Methylation
Acid sphingomyelinase
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