NAD+激酶
巨噬细胞极化
炎症
生物
M2巨噬细胞
坏死性小肠结肠炎
吞噬作用
聚ADP核糖聚合酶
巨噬细胞
烟酰胺腺嘌呤二核苷酸
烟酰胺磷酸核糖转移酶
免疫学
微生物学
生物化学
内科学
酶
医学
聚合酶
体外
作者
Qianyang Liu,Kai Gao,Xionghui Ding,Dandan Mo,Hongjie Guo,Bailin Chen,Bingshan Xia,Cuilian Ye,Gongli Chen,Chunbao Guo
标识
DOI:10.1016/j.biopha.2023.115012
摘要
Nicotinamide phosphoribosyl transferase (NAMPT) is associated with various NAD+ -consuming enzymatic reactions. The precise role in intestinal mucosal immunity in necrotizing enterocolitis (NEC) is not well defined. Here, we examined whether NAMPT inhibition by the highly specific inhibitor FK866 could alleviate intestinal inflammation during the pathogenesis of NEC. In the present study, we showed that NAMPT expression was upregulated in the human terminal ileum of human infants with NEC. FK866 administration attenuated M1 macrophage polarization and relieved the symptoms of experimental NEC pups. FK866 inhibited intercellular NAD+ levels, macrophage M1 polarization, and the expression of NAD+ -dependent enzymes, such as poly (ADP ribose) polymerase 1 (PARP1) and Sirt6. Consistently, the capacity of macrophages to phagocytose zymosan particles, as well as antibacterial activity, were impaired by FK866, whereas NMN supplementation to restore NAD+ levels reversed the changes in phagocytosis and antibacterial activity. In conclusion, FK866 reduced intestinal macrophage infiltration and skewed macrophage polarization, which is implicated in intestinal mucosal immunity, thereby promoting the survival of NEC pups.
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