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皮肤接触免疫调节型抗菌化学物质三氯生会改变小鼠的皮肤屏障完整性和微生物组。

Dermal Exposure to the Immunomodulatory Antimicrobial Chemical Triclosan Alters the Skin Barrier Integrity and Microbiome in Mice.

机构信息

Allergy and Clinical Immunology Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia 26508, USA.

Department of Microbiology, Immunology, and Cell Biology, School of Medicine, West Virginia University, Morgantown, West Virginia 26506, USA.

出版信息

Toxicol Sci. 2021 Nov 24;184(2):223-235. doi: 10.1093/toxsci/kfab111.

Abstract

Triclosan is an antimicrobial chemical used in healthcare settings that can be absorbed through the skin. Exposure to triclosan has been positively associated with food and aeroallergy and asthma exacerbation in humans and, although not directly sensitizing, has been demonstrated to augment the allergic response in a mouse model of asthma. The skin barrier and microbiome are thought to play important roles in regulating inflammation and allergy and disruptions may contribute to development of allergic disease. To investigate potential connections of the skin barrier and microbiome with immune responses to triclosan, SKH1 mice were exposed dermally to triclosan (0.5-2%) or vehicle for up to 7 consecutive days. Exposure to 2% triclosan for 5-7 days on the skin was shown to increase transepidermal water loss levels. Seven days of dermal exposure to triclosan decreased filaggrin 2 and keratin 10 expression, but increased filaggrin and keratin 14 protein along with the danger signal S100a8 and interleukin-4. Dermal exposure to triclosan for 7 days also altered the alpha and beta diversity of the skin and gut microbiome. Specifically, dermal triclosan exposure increased the relative abundance of the Firmicutes family, Lachnospiraceae on the skin but decreased the abundance of Firmicutes family, Ruminococcaceae in the gut. Collectively, these results demonstrate that repeated dermal exposure to the antimicrobial chemical triclosan alters the skin barrier integrity and microbiome in mice, suggesting that these changes may contribute to the increase in allergic immune responses following dermal exposure to triclosan.

摘要

三氯生是一种在医疗环境中使用的抗菌化学物质,可以通过皮肤吸收。人类接触三氯生与食物过敏、空气过敏原和哮喘恶化呈正相关,尽管它本身不会致敏,但已被证明在哮喘的小鼠模型中增强了过敏反应。皮肤屏障和微生物组被认为在调节炎症和过敏反应方面发挥着重要作用,而这些屏障和微生物组的破坏可能导致过敏疾病的发展。为了研究皮肤屏障和微生物组与三氯生免疫反应之间的潜在联系,将 SKH1 小鼠皮肤连续暴露于三氯生(0.5-2%)或载体中,长达 7 天。皮肤暴露于 2%三氯生 5-7 天会增加经皮水分丢失水平。连续 7 天皮肤暴露于三氯生会降低丝聚蛋白 2 和角蛋白 10 的表达,但会增加丝聚蛋白和角蛋白 14 蛋白以及危险信号 S100a8 和白细胞介素-4。连续 7 天皮肤暴露于三氯生还改变了皮肤和肠道微生物组的α和β多样性。具体来说,皮肤暴露于三氯生会增加厚壁菌门、lachnospiraceae 在皮肤上的相对丰度,但会降低肠道中厚壁菌门、ruminococcaceae 的丰度。总的来说,这些结果表明,重复的皮肤暴露于抗菌化学物质三氯生会改变小鼠的皮肤屏障完整性和微生物组,表明这些变化可能导致皮肤暴露于三氯生后过敏免疫反应的增加。

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