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FTY720 attenuates intestinal injury and suppresses inflammation in experimental necrotizing enterocolitis via

Zongtai Feng1, Huiting Zhou1, Shurong Ma1

  • 1Institute of Pediatric Research, Children's Hospital of Soochow University, Suzhou, 215025, China.

Biochemical and Biophysical Research Communications
|October 14, 2018
PubMed

Insights

FTY720 treatment significantly improved survival and reduced intestinal injury in neonatal mice with necrotizing enterocolitis (NEC). This immunomodulatory agent suppressed inflammation and the CXCL5/CXCR2 axis, offering a potential new therapy for NEC.

Area of Science:

  • Neonatal Medicine
  • Immunology
  • Gastroenterology

Background:

  • Necrotizing enterocolitis (NEC) is a leading cause of neonatal mortality.
  • Novel therapeutic strategies for NEC are urgently needed.
  • The immunomodulatory agent FTY720 shows promise in inflammatory conditions.

Purpose of the Study:

  • To investigate the protective effects of FTY720 against experimental necrotizing enterocolitis in neonatal mice.
  • To determine if FTY720 can ameliorate NEC-induced intestinal injury and inflammation.

Main Methods:

  • Experimental NEC was induced in neonatal mice using hyperosmolar formula, hypoxia, and LPS.
  • Mice were treated with FTY720 or a control.
  • Weight loss, mortality, intestinal injury, apoptosis, barrier protein expression, and inflammatory markers were assessed.

Main Results:

  • FTY720 treatment significantly reduced weight loss and improved survival in NEC-challenged mice.
  • FTY720 ameliorated intestinal injury, decreased apoptosis, and normalized intestinal barrier proteins.
  • FTY720 suppressed NEC-induced intestinal and systemic inflammation, including key cytokines and chemokines.
  • FTY720 downregulated the CXCL5/CXCR2 axis in the context of NEC.

Conclusions:

  • FTY720 confers significant protection against experimental NEC-associated lethality in neonatal mice.
  • FTY720 ameliorates intestinal injury and attenuates inflammation in NEC.
  • The protective effects of FTY720 may involve the downregulation of the CXCL5/CXCR2 axis.
Keywords:
CXCL5/CXCR2 axisFTY720Necrotizing enterocolitisNeonatal mice

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