FTY720 attenuates intestinal injury and suppresses inflammation in experimental necrotizing enterocolitis via modulating CXCL5/CXCR2 axis
FTY720 attenuates intestinal injury and suppresses inflammation in experimental necrotizing enterocolitis via modulating CXCL5/CXCR2 axis
复制标题
FTY720 通过调节 CXCL5/CXCR2 轴减轻实验性坏死性小肠结肠炎的肠道损伤并抑制炎症
DOI：
10.1016/j.bbrc.2018.10.013
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发表时间：
2018-11-10
影响因子：
3.1
通讯作者：
Wang, Jian
中科院分区：
文献类型：
--
作者：
Feng, Zongtai;Zhou, Huiting;Wang, Jian
坏死性小肠结肠炎（NEC）仍然是新生儿死亡的主要原因之一，迫切需要新的治疗策略。免疫调节剂FTY 720已被证明在各种炎症性疾病中具有保护作用。在这项研究中，我们假设用FTY 720治疗可以保护实验性NEC。在5日龄C57 BL/6新生小鼠中通过高渗配方喂养加缺氧和脂多糖（LPS）攻击诱导实验性NEC。与对照组相比，NEC的诱导导致显著的体重减轻和高死亡率，而FTY 720治疗显著减弱了NEC攻击的新生小鼠的体重减轻并改善了存活率。FTY 720处理强烈改善NEC诱导的肠损伤，减少回肠组织中的细胞凋亡和肠屏障蛋白的上调。此外，FTY 720治疗消除了NEC引发的肠道和全身炎症，显著减少了炎性细胞因子和趋化因子。此外，FTY 720处理抑制NEC激活的CXCL 5/CXCR 2轴，下调CXCL 5和CXCR 2在mRNA和蛋白水平的表达。因此，我们证明FTY 720通过改善肠损伤和减轻炎症来保护新生小鼠免受NEC相关的致死性，这可能是通过其下调NEC诱导的肠CXCL 5/CXCR 2轴的激活。(C)2018爱思唯尔公司All rights reserved.
Necrotizing enterocolitis (NEC) remains one of the leading causes of death in neonatal infants and new therapeutic strategies for NEC are urgently required. The immunomodulatory agent FTY720 has been shown to have protective effects in various inflammatory diseases. In this study, we hypothesized that treatment with FTY720 confers protection against experimental NEC. Experimental NEC was induced in five-day-old C57BL/6 neonatal mice by hyperosmolar formula feeding plus hypoxia and lipopolysaccharide (LPS) challenges. Induction of NEC resulted in substantial weight loss and high mortality compared to the control group, whereas FTY720 treatment significantly attenuated weight loss and improved survival in NEC-challenged neonatal mice. FTY720 treatment strongly ameliorated NEC-induced intestinal injury with reduced apoptosis and up-regulation of intestinal barrier proteins in the ileal tissues. Furthermore, FTY720 treatment abrogated NEC-initiated intestinal and systemic inflammation with markedly diminished inflammatory cytokines and chemokines. Moreover, FTY720 treatment suppressed NEC-activated CXCL5/CXCR2 axis with down-regulated expression of CXCL5 and CXCR2 at both mRNA and protein levels. Thus, we demonstrate that FTY720 protects neonatal mice against NEC-associated lethality by ameliorating intestinal injury and attenuating inflammation, possibly via its down-regulation of NEC-induced activation of intestinal CXCL5/CXCR2 axis. (C) 2018 Elsevier Inc. All rights reserved.