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首页> 外文期刊>Cell cycle >TNF-alpha induces autophagy through ERK1/2 pathway to regulate apoptosis in neonatal necradzing enterocolitis model cells IEC-6
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TNF-alpha induces autophagy through ERK1/2 pathway to regulate apoptosis in neonatal necradzing enterocolitis model cells IEC-6

机译：TNF-α通过ERK1 / 2途径诱导自噬，以调节新生儿Necradzing内肠癌结肠炎模型细胞IEC-6中的细胞凋亡

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摘要

Necrotizing enterocolitis (NEC) is a potentially fatal illness in premature neonates. Tumor necrosis factor-alpha (TNF-alpha) and autophagy are associated with the pathogenesis of NEC. This study aimed to explore whether TNF-alpha might regulate apoptosis in neonatal NEC model cells IEC-6 via regulation of autophagy. NEC rat model was induced by hand feeding and exposure to asphyxia/cold-stress for histologic examination. The NEC in vitro model (IEC-6/NEC cells) was established by stimulating the intestinal epithelial cell line IEC-6 with lipopolysaccharide (LPS, 100 mu g/mL) for 3 h to investigate the effects of TNF-alpha on IEC-6 proliferation and apoptosis. In this study, NEC rats showed decreased proliferating cell nuclear antigen (PCNA) expression, increased TUNEL-positive cells, higher expression of TNF-alpha, p-ERK1/2, and autophagy-related proteins in rat small intestine compared with their controls. Additionally, the LPS-stimulated IEC-6/NEC cells showed a significantly decreased proliferation and increased apoptosis compared with the control cells. Furthermore, the LPS-stimulated IEC-6/NEC cells exhibited enhanced autophagy level, as evidenced by a dose-dependent increase in Beclin-1 protein expression, LC311/LC31 ratio and accumulation of MDC-positive autophagic vacuoles. Moreover, inhibition of autophagy by wortmannin or LY294002 significantly abolished the LPS-mediated decreased proliferation and increased apoptosis of IEC-6/NEC cells. Results also showed that inhibition of ERK1/2 pathway using UO126 significantly inhibited TNF-alpha-induced autophagy. Furthermore, the TNF-alpha-mediated inhibition of IEC-6 proliferation and promotion of IEC-6 apoptosis was abolished by UO126. Our findings demonstrated that TNF-alpha might induce autophagy through ERK1/2 pathway to regulate apoptosis in neonatal NEC cells IEC-6. Our study enhances our understanding of neonatal NEC pathogenesis.
机译：坏死性小肠结肠炎（NEC）是早产新生儿的潜在致命疾病。肿瘤坏死因子-α（TNF-α）和自噬与NEC的发病机制有关。本研究旨在探讨TNF-α是否可能通过自噬调节调节新生儿NEC模型细胞IEC-6中的细胞凋亡。用手喂养和暴露于窒息/冷应力诱导NEC RAT模型，用于组织学检查。通过用脂多糖（LPS，100μg/ ml）刺激肠上皮细胞系IEC-6来建立NEC体外模型（IEC-6 / NEC细胞）3小时，以研究TNF-α对IEC-的影响6增殖和细胞凋亡。在本研究中，NEC大鼠表现出降低的增殖细胞核抗原（PCNA）表达，增加的TNF-α，P-ERK1 / 2和大鼠小肠中的急性相关蛋白质表达，与其对照组相比，TNF-α，P-ERK1 / 2和自噬相关蛋白质的表达。另外，与对照细胞相比，LPS刺激的IEC-6 / NEC细胞显示出显着降低和增加的细胞凋亡。此外，LPS刺激的IEC-6 / NEC细胞表现出增强的自噬水平，如PECIN-1蛋白表达，LC311 / LC31比和MDC阳性自噬液体的积累的剂量依赖性增加所证明。此外，Wortmannin或Ly294002对自噬的抑制显着消除了LPS介导的增殖和IEC-6 / NEC细胞的凋亡增加。结果还表明，使用UO126的ERK1 / 2途径的抑制显着抑制了TNF-α诱导的自噬。此外，通过UO126废除了TNF-α-介导的IEC-6增殖和促进IEC-6细胞凋亡的抑制。我们的研究结果表明，TNF-α可能会通过ERK1 / 2途径诱导自噬，以调节新生儿NEC细胞IEC-6中的细胞凋亡。我们的研究提高了我们对新生儿NEC发病机制的理解。

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  • 来源
    《Cell cycle》 |2018年第11期|共13页
  • 作者

    Yuan Yuhang; Ding Daokui; Zhang Ning; Xia Ziqiang; Wang Jiaxiang; Yang Heying; Guo Fei; Li Bing;

  • 作者单位

    Zhengzhou Univ Dept Pediat Surg Affiliated Hosp 1 Zhengzhou Henan Peoples R China;

    Zhengzhou Univ Dept Pediat Surg Affiliated Hosp 1 Zhengzhou Henan Peoples R China;

    Zhengzhou Univ Dept Pediat Surg Affiliated Hosp 1 Zhengzhou Henan Peoples R China;

    Zhengzhou Univ Dept Pediat Surg Affiliated Hosp 1 Zhengzhou Henan Peoples R China;

    Zhengzhou Univ Dept Pediat Surg Affiliated Hosp 1 Zhengzhou Henan Peoples R China;

    Zhengzhou Univ Dept Pediat Surg Affiliated Hosp 1 Zhengzhou Henan Peoples R China;

    Zhengzhou Univ Dept Pediat Surg Affiliated Hosp 1 Zhengzhou Henan Peoples R China;

    Zhengzhou Univ Dept Pediat Surg Affiliated Hosp 1 Zhengzhou Henan Peoples R China;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 细胞生物学;
  • 关键词

    TNF-alpha; autophagy; neonatal necrotizing enterocolitis; IEC-6; apoptosis;

    机译：tnf-alpha;自噬;新生儿坏死性小肠结肠炎;IEC-6;细胞凋亡;

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