Staphylococcus aureus Induces Increased Serine Protease Activity in Keratinocytes.
Staphylococcus aureus Induces Increased Serine Protease Activity in Keratinocytes.
复制标题
金黄色葡萄球菌诱导角质形成细胞中丝氨酸蛋白酶活性的增加。
DOI：
10.1016/j.jid.2016.10.008
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发表时间：
2017-02
期刊：
影响因子：
--
通讯作者：
Gallo RL
中科院分区：
文献类型：
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作者：
Williams MR;Nakatsuji T;Sanford JA;Vrbanac AF;Gallo RL
驻留在皮肤上的细菌可以影响皮肤免疫系统的行为，但对这些影响的机制还不完全了解。金黄色葡萄球菌（S.金黄色葡萄球菌）在特应性皮炎（AD）中增加，并可导致疾病严重程度增加。在这项研究中，我们表明，S。金黄色葡萄球菌刺激人角质形成细胞以增加其内源性蛋白酶活性，包括胰蛋白酶活性的特异性增加。这种蛋白酶活性的增加与激肽释放酶（KLK）mRNA表达的增加相一致，KLK 6、13和14在暴露于S.金黄色。在S.金黄色葡萄球菌暴露阻断了蛋白酶活性的增加。角质形成细胞暴露于S.金黄色葡萄球菌显示桥粒芯糖蛋白-1（DSG-1）和聚丝蛋白（FLG）的降解增强，而针对KLK 6、KLK 13和KLK 14的siRNA部分阻断了这种降解。这些数据说明S.金黄色葡萄球菌通过刺激内源性蛋白水解活性直接影响皮肤屏障的完整性，并定义了一种以前未知的机制，金黄色葡萄球菌可能影响皮肤疾病。
Bacteria that reside on the skin can influence the behavior of the cutaneous immune system, but the mechanisms responsible for these effects are incompletely understood. Colonization of the skin by Staphylococcus aureus (S. aureus) is increased in atopic dermatitis (AD) and can result in increased severity of the disease. In this study we show that S. aureus stimulates human keratinocytes to increase their endogenous protease activity, including specific increases in trypsin activity. This increased protease activity coincided with increased expression of mRNA for kallikreins (KLKs), with KLK6, 13, and 14 showing the greatest induction after exposure to S. aureus. Suppression of mRNA for these KLKs in keratinocytes by targeted siRNA silencing prior to S. aureus exposure blocked the increase in protease activity. Keratinocytes exposed to S. aureus showed enhanced degradation of desmoglein-1 (DSG-1) and filaggrin (FLG) while siRNA for KLK6, KLK13, and KLK14 partially blocked this degradation. These data illustrate how S. aureus directly influences the skin barrier integrity by stimulating endogenous proteolytic activity and defines a previously unknown mechanism by which S. aureus may influence skin diseases.