Extracellular nicotinamide phosphoribosyltransferase boosts IFNγ-induced macrophage polarization independently of TLR4.

ABSTRACT: Nicotinamide phosphoribosyltransferase (NAMPT), alongside being a crucial enzyme in NAD synthesis, has been shown to be a secreted protein (eNAMPT), whose levels are increased in patients affected by immune-mediated disorders. Accordingly, preclinical studies have highlighted that eNAMPT participates in the pathogenesis of several inflammatory diseases. Herein, we analyzed the effects of eNAMPT on macrophage-driven inflammation. RNAseq analysis of peritoneal macrophages (PECs) demonstrates that eNAMPT triggers an M1-skewed transcriptional program, and this effect is not dependent on the enzymatic activity. Noteworthy, both in PECs and in human monocyte-derived macrophages, eNAMPT selectively boosts IFNγ-driven transcriptional activation via STAT1/3 phosphorylation. Importantly, the

SUBMITTER: Colombo G 

PROVIDER: S-EPMC8990213 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature