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

Qianyang Liu; Kai Gao; Xionghui Ding; Dandan Mo; Hongjie Guo; Bailin Chen; Bingshan Xia; Cuilian Ye; Gongli Chen; Chunbao Guo

Biomedicine & Pharmacotherapy (Sep 2023)

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

Qianyang Liu,
Kai Gao,
Xionghui Ding,
Dandan Mo,
Hongjie Guo,
Bailin Chen,
Bingshan Xia,
Cuilian Ye,
Gongli Chen,
Chunbao Guo

Affiliations

Qianyang Liu: Department of Pediatrics, Chongqing Health Center for Women and Children, Chongqing, China; Department of Pediatric Surgery, Chongqing Health Center for Women and Children, Chongqing Medical University, Chongqing 400054, China; Department of Obstetrics and Gynecology, Women and Chidren's Hospital, Chongqing Medical University, Chongqing, China
Kai Gao: Department of Pediatrics, Chongqing Health Center for Women and Children, Chongqing, China; Department of Pediatric Surgery, Chongqing Health Center for Women and Children, Chongqing Medical University, Chongqing 400054, China
Xionghui Ding: Department of Burn, Children’s Hospital of Chongqing Medical University, Chongqing, China
Dandan Mo: Department of Pediatric Surgery, Chongqing Health Center for Women and Children, Chongqing Medical University, Chongqing 400054, China
Hongjie Guo: Department of anesthesiology, Children’s Hospital of Chongqing Medical University, Chongqing, China
Bailin Chen: Department of General Surgery, Children’s Hospital of Chongqing Medical University, Chongqing, China
Bingshan Xia: Department of Pediatrics, Chongqing Health Center for Women and Children, Chongqing, China; Department of Pediatric Surgery, Chongqing Health Center for Women and Children, Chongqing Medical University, Chongqing 400054, China; Department of Obstetrics and Gynecology, Women and Chidren's Hospital, Chongqing Medical University, Chongqing, China
Cuilian Ye: School of Pharmacy and Bioengineering, Chongqing University of Technology, Chongqing 400054, China
Gongli Chen: Department of Pediatrics, Chongqing Health Center for Women and Children, Chongqing, China; Department of Pediatric Surgery, Chongqing Health Center for Women and Children, Chongqing Medical University, Chongqing 400054, China; Department of Obstetrics and Gynecology, Women and Chidren's Hospital, Chongqing Medical University, Chongqing, China; Correspondence to: Department of Obstetrics and Gynecology, Chongqing Health Center for Women and Children, Women and Children’s Hospital of Chongqing Medical University, 120 Longshan Rd, Chongqing 401147, China.
Chunbao Guo: Department of Pediatrics, Chongqing Health Center for Women and Children, Chongqing, China; Department of Pediatric Surgery, Chongqing Health Center for Women and Children, Chongqing Medical University, Chongqing 400054, China; Department of Obstetrics and Gynecology, Women and Chidren's Hospital, Chongqing Medical University, Chongqing, China; Correspondence to: Department of Pediatrics, Chongqing Health Center for Women and Children, Women and Children’s Hospital of Chongqing Medical University, 120 Longshan Rd, Chongqing 401147, China.

Journal volume & issue: Vol. 165
p. 115012

Abstract

Read online

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.

Published in Biomedicine & Pharmacotherapy

ISSN: 0753-3322 (Print); 1950-6007 (Online)
Publisher: Elsevier
Country of publisher: France
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: https://www.journals.elsevier.com/biomedicine-and-pharmacotherapy

About the journal

Abstract

Keywords