Particulate matter causes skin barrier dysfunction
Particulate matter causes skin barrier dysfunction
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DOI：
10.1172/jci.insight.145185
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发表时间：
2021-03-08
期刊：
影响因子：
8
通讯作者：
Ahn, Kangmo
中科院分区：
文献类型：
--
作者：
Kim, Byung Eui;Kim, Jihyun;Ahn, Kangmo
人们对颗粒物 (PM) 对皮肤屏障功能产生有害影响的分子机制知之甚少。本研究在体外和体内研究了 PM2.5 对聚丝蛋白 (FLG) 和皮肤屏障功能的影响。当研究对象从 PM2.5 含量较低的丹佛市搬到 PM2.5 含量较高的首尔地区时，研究对象的皮肤胶带剥离样本中的 FLG 降解产物（包括吡咯烷酮羧酸、尿刊酸 (UCA) 和顺/反式 UCA）水平显着降低。实验上，在首尔收集的 PM2.5 抑制 FLG、loricrin、keratin-1、desmocollin-1 和 corneodesmosin，但不调节角质形成细胞培养物中的外皮蛋白或 Claudin-1。此外，在人类皮肤等同物和经 PM2.5 处理的小鼠皮肤中，FLG 蛋白表达受到抑制。我们证明这一过程是由 PM2.5 诱导的 TNF-α 介导的，并且依赖于芳烃受体。 PM2.5 暴露会损害皮肤屏障功能，导致经皮水分流失增加，并增强 FITC-葡聚糖在器官和小鼠皮肤中的渗透。 PM2.5诱导的TNF-α导致皮肤中FLG缺乏，随后引起皮肤屏障功能障碍。 PM2.5 暴露导致的皮肤屏障受损可能会导致特应性皮炎等过敏性疾病的发生和恶化。
The molecular mechanisms that underlie the detrimental effects of particulate matter (PM) on skin barrier function are poorly understood. In this study, the effects of PM2.5 on filaggrin (FLG) and skin barrier function were investigated in vitro and in vivo. The levels of FLG degradation products, including pyrrolidone carboxylic acid, urocanic acid (UCA), and cis/trans-UCA, were significantly decreased in skin tape stripping samples of study subjects when they moved from Denver, an area with low PM2.5, to Seoul, an area with high PM2.5 count. Experimentally, PM2.5 collected in Seoul inhibited FLG, loricrin, keratin-1, desmocollin-1, and corneodesmosin but did not modulate involucrin or claudin-1 in keratinocyte cultures. Moreover, FLG protein expression was inhibited in human skin equivalents and murine skin treated with PM2.5. We demonstrate that this process was mediated by PM2.5-induced TNF-alpha and was aryl hydrocarbon receptor dependent. PM2.5 exposure compromised skin barrier function, resulting in increased transepidermal water loss, and enhanced the penetration of FITC-dextran in organotypic and mouse skin. PM2.5-induced TNF-alpha caused FLG deficiency in the skin and subsequently induced skin barrier dysfunction. Compromised skin barrier due to PM2.5 exposure may contribute to the development and the exacerbation of allergic diseases such as atopic dermatitis.