Variant innate immune responses of mammary epithelial cells to challenge by Staphylococcus aureus, Escherichia coli and the regulating effect of taurine on these bioprocesses
Variant innate immune responses of mammary epithelial cells to challenge by Staphylococcus aureus, Escherichia coli and the regulating effect of taurine on these bioprocesses
复制标题
乳腺上皮细胞对金黄色葡萄球菌、大肠杆菌攻击的变异先天免疫反应以及牛磺酸对这些生物过程的调节作用
DOI：
10.1016/j.freeradbiomed
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发表时间：
2016
影响因子：
7.4
通讯作者：
Yin YL
中科院分区：
文献类型：
--
作者：
Zheng LH;Xu YY;Lu JY;Liu M;Dai B;Miao JF;Yin YL
大肠杆菌（E. coli）和金黄色葡萄球菌（S. aureus）分别是引起亚临床和临床牛乳腺炎的重要病原体。牛磺酸是一种存在于动物组织中的有机酸，已用于治疗各种浅表感染和慢性炎症。我们用大肠杆菌或金黄色葡萄球菌攻击牛乳腺上皮细胞 (MEC) 系 (MAC-T) 或小鼠乳腺上皮细胞系 (EpH4-Ev)，并比较 MEC 对这两种病原体的反应。我们还研究了牛磺酸对这些反应的调节作用。受体分析表明，TLR2 和 TLR4 在接触大肠杆菌或金黄色葡萄球菌后都会上调。牛磺酸预处理在一定程度上抑制了上调。大肠杆菌和金黄色葡萄球菌刺激的 ROS 水平相当，而牛磺酸预处理可以抑制这种水平。大肠杆菌感染引起 iNOS 表达的巨大变化。牛磺酸显着降低金黄色葡萄球菌攻击组中 iNOS 的表达。蛋白质微阵列表明，在大肠杆菌或金黄色葡萄球菌攻击后，分别有 32/40 和 8/40 的炎症分子/介质增加。大多数分子的倍数变化在大肠杆菌感染组中高于金黄色葡萄球菌感染组。牛磺酸对两种细菌感染的炎症状况都有负向调节作用。牛磺酸预处理可下调与 TLR 激活相关的促炎细胞因子（如 TNF-α）。 TAK-242 和 OxPAPC 对大肠杆菌攻击的细胞因子/分子表达谱的影响与金黄色葡萄球菌攻击不同。 TLR 激活介导的一些重要因子（MyD88、TNF-α、IL-1β、iNOS 和 IL-6）在蛋白质微阵列或特殊测定（PCR/试剂盒）或两者中均受到抑制。 TAK-242 抑制 ROS 产生和 NAGase 活性，类似于牛磺酸在大肠杆菌攻击组中的作用。反映体内氧化应激的3个指标（T-AOC、SOD、MDA）检测表明，牛磺酸提高了细胞的抗氧化能力。我们得出结论，牛磺酸可以通过影响TLR介导的信号通路和提高细胞的抗氧化能力来调节大肠杆菌感染期间的炎症反应并防止细胞损伤。在金黄色葡萄球菌感染中，牛磺酸的抗氧化能力可能是抵抗炎症的主要手段。这项研究使人们更好地了解大肠杆菌和金黄色葡萄球菌乳腺炎的炎症机制，并为预防这种疾病提供了假定的策略。
Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) are important pathogens causing subclinical and clinical bovine mastitis, respectively. Taurine, an organic acid found in animal tissues, has been used for the treatment of various superficial infections and chronic inflammations. We challenged a bovine mammary epithelial cell (MEC) line (MAC-T) or a mouse mammary epithelial cell line (EpH4-Ev) with either E.coli or S. aureus and compared the responses of MECs to these 2 pathogens. We also examined the regulatory effects of taurine on these responses. Receptor analyses showed that both TLR2 and TLR4 are upregulated upon exposure to either E. coli or S. aureus. Taurine pre-treatment dampened upregulation to some extent. E. coli and S. aureus stimulated comparable levels of ROS, which could be inhibited by taurine pre-treatment. E. coli infection elicited a dramatic change in iNOS expression. Taurine significantly decreased iNOS expression in the S. aureus challenged group. Protein microarray demonstrated that 32/40 and 8/40 inflammatory molecules/mediators were increased after E. coli or S. aureus challenge, respectively. The fold changes of most molecules were higher in the E. coli infection group than that in the S. aureus infection group. Taurine negatively regulated the inflammatory profile in both bacterial infections. Proinflammatory cytokines (such as TNF-α) connected with TLR activation were down-regulated by taurine pre-treatment. The influence of TAK-242 and OxPAPC on cytokine/molecule expression profiles to E. coli challenge are different than to S. aureus. Some important factors (MyD88, TNF-α, IL-1β, iNOS and IL-6) mediated by TLR activation were suppressed either in protein microarray or special assay (PCR/kits) or both. TAK-242 restrained ROS production and NAGase activity similar to the effect of taurine in E. coli challenge groups. The detection of 3 indices (T-AOC, SOD and MDA) reflecting oxidative stress in vivo, showed that taurine improved the antioxidant ability of cells. We conclude that taurine can regulate the inflammatory response during infection with E. coli and prevent cell damage by affecting the signaling pathways mediated by TLRs and by improving the antioxidant ability of cells. In S. aureus infections,taurine's antioxidant ability may be the primary means of resistance to inflammation. This study provides a better understanding of the inflammatory mechanisms of E. coli and S. aureus mastitis, and it provides a putative strategy for the prevention of this disease.