首页|NLRP3 activation in macrophages promotes acute intestinal injury in neonatal necrotizing enterocolitis

NLRP3 activation in macrophages promotes acute intestinal injury in neonatal necrotizing enterocolitis

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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.

Caspase-1Interleukin-1βMacrophageNecrotizing enterocolitisNLRP3

Bo Shi、Cheng-Jie Lyu、Zhen-Kai Le、Hao-Sen Ji、Yi Xiao、Yuan-Yuan Zhang、Shou-Jiang Huang、Lin-Jun Yu、Qiang Shu、Jin-Fa Tou、Deng-Ming Lai

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Department of Neonatal Surgery,Children's Hospital,Zhejiang University School of Medicine,National Clinical Research Center for Child Health,Hangzhou 310052,China

Department of Pulmonology,Children's Hospital,Zhejiang University School of Medicine,National Clinical Research Center for Child Health,Hangzhou 310052,China

Department of Thoracic and Cardiovascular Surgery,Children's Hospital,Zhejiang University School of Medicine,National Clinical Research Center for Child Health,Hangzhou 310052,China

National Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNatural Science Foundation of Zhejiang ProvinceNatural Science Foundation of Zhejiang ProvinceFoundation for The Top-Notch Youth Talent Cultivation Project of Independent Design Project of National Clinical Research CenterSpecial Fund for the Incubation of Young Clinical Scientist,Children's Hospital,Zhejiang University School of Medicine

819019898227219182171699LY21H150005LY22H040006Q21B0007CHZJU2022YS002

2024

10.1007/s12519-023-00727-5

世界儿科杂志(英文版)

世界儿科杂志(英文版)

CSTPCD
ISSN：
年,卷(期)：2024.20(2)
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