Intracellular NAD⁺ Depletion Confers a Priming Signal for NLRP3 Inflammasome Activation.

ABSTRACT: Nicotinamide adenine dinucleotide (NAD⁺) is an important cofactor in many redox and non-redox NAD⁺-consuming enzyme reactions. Intracellular NAD⁺ level steadily declines with age, but its role in the innate immune potential of myeloid cells remains elusive. In this study, we explored whether NAD⁺ depletion by FK866, a highly specific inhibitor of the NAD salvage pathway, can affect pattern recognition receptor-mediated responses in macrophages. NAD⁺-depleted mouse bone marrow-derived macrophages (BMDMs) exhibited similar levels of proinflammatory cytokine production in response to LPS or poly (I:C) stimulation compared with untreated cells. Instead, FK866 facilitated robust caspase-1 activation in BMDMs in the presence of NLRP3-activat

SUBMITTER: Shim DW 

PROVIDER: S-EPMC8722528 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature