1887

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Volume 69, Issue 5

induces necrotizing enterocolitis by regulating NLRP3 inflammasome expression via TLR4 Free

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.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): Cronobacter sakazakii , Gasdermin D , necrotizing enterocolitis and NLRP3
Funding
This study was supported by the:
  • Youth Project of The Dean’s Fund of Nanfang Hospital of Southern Medical University (Award 2017C50)
    • Principle Award Recipient: Wei Shen
  • Guangdong Basic and Applied Basic Research Foundation (Award 2019A1515011759)
    • Principle Award Recipient: Hongying Fan
  • Science and Technology Program of Guangdong (Award 2018B020205002)
    • Principle Award Recipient: Hongying Fan
  • National Natural Science Foundation of China (Award 31872630)
    • Principle Award Recipient: Hongying Fan
© 2020 The Authors
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2020-03-25
2024-12-03
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Cronobacter sakazakii induces necrotizing enterocolitis by regulating NLRP3 inflammasome expression via TLR4
J. Med. Microbiol. 69, 748 (2020); https://doi.org/10.1099/jmm.0.001181
/content/journal/jmm/10.1099/jmm.0.001181
/content/journal/jmm/10.1099/jmm.0.001181
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