炎症
炎症体
TLR4型
调解人
Toll样受体
细胞生物学
化学
CD14型
烟酰胺磷酸核糖转移酶
巨噬细胞
受体
细胞外
先天免疫系统
免疫学
NAD+激酶
生物
体外
生物化学
酶
作者
Antonella Managò,Valentina Audrito,Francesca Mazzola,Leonardo Sorci,Federica Gaudino,Katiuscia Gizzi,Nicoletta Vitale,Danny Incarnato,Gabriele Minazzato,Alice Ianniello,Antonio Varriale,Sabato D’Auria,Giulio Mengozzi,Gianfranco Politano,Salvatore Oliviero,Nadia Raffaelli,Silvia Deaglio
标识
DOI:10.1038/s41467-019-12055-2
摘要
Abstract Damage-associated molecular patterns (DAMPs) are molecules that can be actively or passively released by injured tissues and that activate the immune system. Here we show that nicotinate phosphoribosyltransferase (NAPRT), detected by antibody-mediated assays and mass spectrometry, is an extracellular ligand for Toll-like receptor 4 (TLR4) and a critical mediator of inflammation, acting as a DAMP. Exposure of human and mouse macrophages to NAPRT activates the inflammasome and NF-κB for secretion of inflammatory cytokines. Furthermore, NAPRT enhances monocyte differentiation into macrophages by inducing macrophage colony-stimulating factor. These NAPRT-induced effects are independent of NAD-biosynthetic activity, but rely on NAPRT binding to TLR4. In line with our finding that NAPRT mediates endotoxin tolerance in vitro and in vivo, sera from patients with sepsis contain the highest levels of NAPRT, compared to patients with other chronic inflammatory conditions. Together, these data identify NAPRT as a endogenous ligand for TLR4 and a mediator of inflammation.
科研通智能强力驱动
Strongly Powered by AbleSci AI