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Abstract

Neonatal infection with can cause severe intestinal damage and necrotizing enterocolitis (NEC). The inflammasome and Toll-like receptors mediate intestinal damage caused by other intestinal pathogens causing NEC, but the exact mechanism is unclear.

We evaluated the molecular mechanisms underlying -induced NEC.

The effects of treatment on two cell lines and a Sprague–Dawley rat model of NEC were evaluated by a cell death assay, western blot and real-time PCR analyses of the NLRP3 inflammasome and downstream factors, and observation of cell and intestinal damage.

caused cellular damage , as well as intestinal damage in an animal model. NLRP3, caspase-1, TLR4 and MyD88, as well as the downstream factor IL-1β, were upregulated in -infected J774A.1 and HT-29 cells. Western blotting showed that infected J774A.1 and HT-29 cells and the NEC rat model had higher expression levels of N-terminal gasdermin D (GSDMD) compared with those in the control groups. and its components promote NF-κB expression via the TLR4/MyD88 signalling pathway, thereby regulating the NLRP3 inflammasome and mediating GSDMD cleavage, resulting in pyroptosis-induced intestinal damage.

We found that upregulates NF-κB via TLR4/MyD88 to promote activation of the NLRP3 inflammasome, leading to the up-regulation of downstream caspase-1, release of IL-1β, GSDMD-mediated pyroptosis and development of NEC. These findings clarify the mechanisms by which contributes to NEC.

Funding
This study was supported by the:
  • Wei Shen , Youth Project of The Dean’s Fund of Nanfang Hospital of Southern Medical University , (Award 2017C50)
  • Hongying Fan , Guangdong Basic and Applied Basic Research Foundation , (Award 2019A1515011759)
  • Hongying Fan , Science and Technology Program of Guangdong , (Award 2018B020205002)
  • Hongying Fan , National Natural Science Foundation of China , (Award 31872630)
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/content/journal/jmm/10.1099/jmm.0.001181
2020-03-25
2020-04-01
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