NAMPT inhibition relieves intestinal inflammation by regulating macrophage activation in experimental necrotizing enterocolitis

作者全名："Liu, Qianyang; Gao, Kai; Ding, Xionghui; Mo, Dandan; Guo, Hongjie; Chen, Bailin; Xia, Bingshan; Ye, Cuilian; Chen, Gongli; Guo, Chunbao"

作者地址："[Liu, Qianyang; Gao, Kai; Xia, Bingshan; Chen, Gongli; Guo, Chunbao] Chongqing Hlth Ctr Women & Children, Dept Pediat, Chongqing, Peoples R China; [Liu, Qianyang; Gao, Kai; Mo, Dandan; Xia, Bingshan; Chen, Gongli; Guo, Chunbao] Chongqing Med Univ, Chongqing Hlth Ctr Women & Children, Dept Pediat Surg, Chongqing 400054, Peoples R China; [Ding, Xionghui] Chongqing Med Univ, Childrens Hosp, Dept Burn, Chongqing, Peoples R China; [Guo, Hongjie] Chongqing Med Univ, Childrens Hosp, Dept anesthesiol, Chongqing, Peoples R China; [Chen, Bailin] Chongqing Med Univ, Childrens Hosp, Dept Gen Surg, Chongqing, Peoples R China; [Ye, Cuilian] Chongqing Univ Technol, Sch Pharm & Bioengn, Chongqing 400054, Peoples R China; [Liu, Qianyang; Xia, Bingshan; Chen, Gongli; Guo, Chunbao] Chongqing Med Univ, Women & Chidrens Hosp, Dept Obstet & Gynecol, Chongqing, Peoples R China; [Chen, Gongli] Northeastern Univ, Dept Phys Therapy Movement & Rehabil Sci, 360 Huntington Ave,457 Richards Hall, Boston, MA 02115 USA; [Guo, Chunbao] Chongqing Med Univ, Women & Childrens Hosp, Chongqing Hlth Ctr Women & Children, Dept Pediat, 120 Longshan Rd, Chongqing 401147, Peoples R China"

通信作者："Chen, GL (通讯作者)，Northeastern Univ, Dept Phys Therapy Movement & Rehabil Sci, 360 Huntington Ave,457 Richards Hall, Boston, MA 02115 USA.; Guo, CB (通讯作者)，Chongqing Med Univ, Women & Childrens Hosp, Chongqing Hlth Ctr Women & Children, Dept Pediat, 120 Longshan Rd, Chongqing 401147, Peoples R China."

来源：BIOMEDICINE & PHARMACOTHERAPY

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:001023551000001

JCR分区：Q1

影响因子：6.9

年份：2023

卷号：165

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：NEC; NAMPT; FK866; Macrophage

摘要："Nicotinamide phosphoribosyl transferase (NAMPT) is associated with various NAD+ -consuming enzymatic re-actions. 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 in-testinal macrophage infiltration and skewed macrophage polarization, which is implicated in intestinal mucosal immunity, thereby promoting the survival of NEC pups."

基金机构："National Natural Science Foundation of China [30973440, 30770950]; Ministry of Key Laboratory of Child Development and Disorders [YBRP2021XX]; key project of the Chongqing Natural Science Foundation [cstc2020jcyj-msxmX0326, CSTB2022NSCQ-MSX0819]"

基金资助正文："The research was supported by the National Natural Science Foundation of China (No: 30973440, 30770950), the Youth Basic Research Project from the Ministry of Key Laboratory of Child Development and Disorders (No. YBRP2021XX) and the key project of the Chongqing Natural Science Foundation (cstc2020jcyj-msxmX0326, CSTB2022NSCQ-MSX0819)."