Abstract
Background Macrophages are involved in various immune inflammatory disease conditions.This study aimed to investigate the role and mechanism of macrophages in regulating acute intestinal injury in neonatal necrotizing enterocolitis(NEC).Methods CD68,nucleotide-binding oligomerization domain,leucine-rich repeat,and pyrin domain-containing 3(NLRP3),cysteine aspartate-specific protease-1(caspase-1),and interleukin-1β(IL-1 β)in paraffin sections of intestinal tissues from NEC and control patients were detected with immunohistochemistry,immunofluorescence,and western blot.Hypertonic pet milk,hypoxia and cold stimulation were used to establish a mouse(wild type and Nlrp3-/-)model of NEC.The mouse macrophage(RAW 264.7)and rat intestinal epithelial cell-6 lines were also cultured followed by various treatments.Mac-rophages,intestinal epithelial cell injuries,and IL-1β release were determined.Results Compared to the gut"healthy"patients,the intestinal lamina propria of NEC patients had high macrophage infil-tration and high NLRP3,caspase-1,and IL-1β levels.Furthermore,in vivo,the survival rate of Nlrp3/-NEC mice was dramatically improved,the proportion of intestinal macrophages was reduced,and intestinal injury was decreased compared to those of wild-type NEC mice.NLRP3,caspase-1,and IL-1β derived from macrophages or supernatant from cocultures of macrophages and intestinal epithelial cells also caused intestinal epithelial cell injuries.Conclusions Macrophage activation may be essential for NEC development.NLRP3/caspase-1/IL-1β cellular signals derived from macrophages may be the underlying mechanism of NEC development,and all these may be therapeutic targets for developing treatments for NEC.
基金项目
National Natural Science Foundation of China(81901989)
National Natural Science Foundation of China(82272191)
National Natural Science Foundation of China(82171699)
Natural Science Foundation of Zhejiang Province(LY21H150005)
Natural Science Foundation of Zhejiang Province(LY22H040006)
Foundation for The Top-Notch Youth Talent Cultivation Project of Independent Design Project of National Clinical Research Center(Q21B0007)
Special Fund for the Incubation of Young Clinical Scientist,Children's Hospital,Zhejiang University School of Medicine(CHZJU2022YS002)
NETL
NSTL
万方数据