Caspase‐1‐dependent mechanism mediating the harmful impacts of the quorum‐sensing molecule N‐(3‐oxo‐dodecanoyl)‐l‐homoserine lactone on the intestinal cells
Caspase‐1‐dependent mechanism mediating the harmful impacts of the quorum‐sensing molecule N‐(3‐oxo‐dodecanoyl)‐l‐homoserine lactone on the intestinal cells
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DOI：
10.1002/jcp.27132
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发表时间：
2018-11
影响因子：
5.6
通讯作者：
S. Tao;Qinwei Sun;L. Cai;Y. Geng;C. Hua;Y. Ni;R. Zhao
中科院分区：
文献类型：
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作者：
S. Tao;Qinwei Sun;L. Cai;Y. Geng;C. Hua;Y. Ni;R. Zhao
N-（3-氧代十二烷酰基）-l-高丝氨酸内酯（3-氧代-C12-HSL）是胃肠道中革兰氏阴性菌产生的一种群体感应（QS）分子，对宿主细胞有不良影响。我们之前的研究表明，3-oxo-C12-HSL通过细胞凋亡诱导细胞活力降低，并最终破坏LS 174 T杯状细胞的粘蛋白合成。然而，细胞凋亡的分子机制以及细胞凋亡是否参与了这一过程仍不清楚。本研究从caspase信号通路和无菌性炎症两个方面探讨3-oxo-C12-HSL对LS 174 T杯状细胞的损伤作用。我们的数据表明，3-oxo-C12-HSL是氧化应激的主要诱导剂，其表现为高水平的细胞内活性氧（ROS）。然而，对氧磷酶2抑制剂TQ 416可以有效地阻断氧化应激。较高的ROS水平是激活caspase-1和3级联信号通路的触发因素。阻断ROS合成和caspase-1和3级联反应可以明显挽救3-oxo-C12-HSL处理后的LS 174 T细胞的活力。我们还发现，3-oxo-C12-HSL处理诱导了具有较高水平的ROS和半胱天冬酶活化的细胞，促炎细胞因子的异常表达;然而，TLRs-NF-κB通路的阻断不能恢复细胞活力和分泌功能。这些数据共同表明，3-oxo-C12-HSL暴露诱导对LS 174 T杯状细胞的细胞活力和分泌功能的损害，这是由氧化应激、细胞凋亡和无菌炎症介导的。总体而言，本研究中的数据将有助于更好地了解某些QS分子对宿主细胞的有害影响及其潜在机制。
N‐(3‐oxododecanoyl)‐l‐homoserine lactone (3‐oxo‐C12‐HSL), a quorum‐sensing (QS) molecule produced by Gram‐negative bacteria in the gastrointestinal tract, adversly impacts host cells. Our previous study demonstrated that 3‐oxo‐C12‐HSL induced a decrease in cell viability via cell apoptosis and eventually disrupted mucin synthesis from LS174T goblet cells. However, the molecular mechanism underlying cell apoptosis and whether pyroptosis was involved in this process are still unknown. In this study, we emphasized on the caspases signal pathway and sterile inflammation to reveal the harmful effects of 3‐oxo‐C12‐HSL on LS174T goblet cells. Our data showed that 3‐oxo‐C12‐HSL is a major inducer of oxidative stress indicated by a high level of intracellular reactive oxygen species (ROS). However, TQ416, an inhibitor of paraoxonase 2, can effectively block oxidative stress. A higher ROS level is the trigger for activating the caspase‐1 and 3 cascade signal pathways. Blockade of ROS synthesis and caspase‐1 and 3 cascades can obviously rescue the viability of LS174T cells after 3‐oxo‐C12‐HSL treatment. We also found that paralleled with a higher level of ROS and caspases activation, an abnormal expression of proinflammatory cytokines was induced by 3‐oxo‐C12‐HSL treatment; however, the blockage of TLRs‐NF‐κB pathway cannot restore cell viability and secretary function. These data collectively indicate that 3‐oxo‐C12‐HSL exposure induces damages to cell viability and secretary function of LS174T goblet cells, which is mediated by oxidative stress, cell apoptosis, and sterile inflammation. Overall, the data in this study will provide a better understanding of the harmful impacts of some QS molecules on host cells and their underlying mechanism.