Yao Fu1, Li-Ping Chen1, Peng Li1, Zhi-Bao Lv1. 1. Department of General Surgery, Shanghai Children's Hospital, Shanghai Jiao Tong University, Shanghai, China.
Abstract
Background: Necrotizing enterocolitis (NEC)-the leading cause of neonatal death-has been shown to be associated with an excessive inflammatory response of the intestines. Fingolimod has shown efficacy in treating many inflammatory diseases. In this study, we aimed to explore the protective effects of fingolimod on a mouse model of NEC. Methods: Experimental NEC was induced in 5-day-old C57BL/6 neonatal mice. Many methods include Hematoxylin and eosin (H&E), immunofluorescence staining, polymerase chain reaction (PCR) and western blot were used to evaluate the degreed of inflammation of NEC. A model of T-cell co-culture system in vitro was used to explain the way Fingolimod acted on T cell. We also detected the NEC associated brain injury by immunofluorescence staining. Results: Fingolimod treatment ameliorated NEC-induced intestinal injury, reduced inflammatory T cell infiltration, and regulated the balance between T helper 17 (Th17) and regulatory T cells in intestinal tissues. In addition, fingolimod treatment was found to blunt the pro-inflammatory phenotype of activated macrophages and decrease interleukin-17 (IL-17) secretion. Fingolimod treatment also ameliorated NEC-induced neuroinflammation. Conclusions: Fingolimod can protect neonatal mice from NEC-related death by ameliorating intestinal injury and attenuating excessive inflammatory responses. These effects may be mediated through an improved Th17/Treg balance, which may result from direct and indirect effects of fingolimod on T cell infiltration and macrophage differentiation. 2022 Translational Pediatrics. All rights reserved.
Background: Necrotizing enterocolitis (NEC)-the leading cause of neonatal death-has been shown to be associated with an excessive inflammatory response of the intestines. Fingolimod has shown efficacy in treating many inflammatory diseases. In this study, we aimed to explore the protective effects of fingolimod on a mouse model of NEC. Methods: Experimental NEC was induced in 5-day-old C57BL/6 neonatal mice. Many methods include Hematoxylin and eosin (H&E), immunofluorescence staining, polymerase chain reaction (PCR) and western blot were used to evaluate the degreed of inflammation of NEC. A model of T-cell co-culture system in vitro was used to explain the way Fingolimod acted on T cell. We also detected the NEC associated brain injury by immunofluorescence staining. Results: Fingolimod treatment ameliorated NEC-induced intestinal injury, reduced inflammatory T cell infiltration, and regulated the balance between T helper 17 (Th17) and regulatory T cells in intestinal tissues. In addition, fingolimod treatment was found to blunt the pro-inflammatory phenotype of activated macrophages and decrease interleukin-17 (IL-17) secretion. Fingolimod treatment also ameliorated NEC-induced neuroinflammation. Conclusions: Fingolimod can protect neonatal mice from NEC-related death by ameliorating intestinal injury and attenuating excessive inflammatory responses. These effects may be mediated through an improved Th17/Treg balance, which may result from direct and indirect effects of fingolimod on T cell infiltration and macrophage differentiation. 2022 Translational Pediatrics. All rights reserved.
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