Mechanisms by which psychologic stress alters cutaneous permeability barrier homeostasis and stratum corneum integrity
Mechanisms by which psychologic stress alters cutaneous permeability barrier homeostasis and stratum corneum integrity
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DOI：
10.1111/j.0022-202x.2005.23589.x
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发表时间：
2005-03-01
影响因子：
6.5
通讯作者：
Feingold, KR
中科院分区：
文献类型：
--
作者：
Choi, EH;Brown, BE;Feingold, KR
尽管许多皮肤病，包括牛皮癣和特应性皮炎，都会受到心理应激 (PS) 的不利影响，但 PS 和疾病表现之间的病理生理学联系仍不清楚。最近的研究表明，PS 诱导的通透性屏障稳态改变是由内源性糖皮质激素增加介导的。在这里，我们评估了 PS 改变角质层 (SC) 功能的机制。失眠心理压力 (IPS) 改变了屏障稳态和 SC 完整性。 IPS 减少表皮细胞增殖，损害表皮分化，并降低角化桥粒 (CD) 的密度和大小，这与 CD 蛋白（例如桥粒芯糖蛋白 1）的降解有关。屏障受损与层状体（LB）的产生和分泌减少有关，而层状体（LB）的产生和分泌减少又可能归因于表皮脂质从头合成的减少。局部生理脂质（等摩尔胆固醇、神经酰胺和游离脂肪酸）使 IPS 小鼠的屏障稳态和 SC 完整性正常化，进一步证明脂质缺乏导致了这些功能异常。因此，PS 对表皮脂质合成的抑制导致 LB 形成和分泌减少，以及 CD 减少，从而损害渗透性屏障稳态和 SC 完整性。这些研究表明，使用表皮生理脂质进行局部治疗可能有益于应激诱发的屏障相关皮肤病，例如牛皮癣和特应性皮炎。
Although many skin disorders, including psoriasis and atopic dermatitis, are adversely affected by psychologic stress (PS), the pathophysiologic link between PS and disease expression remains unclear. Recent studies demonstrated PS-induced alterations in permeability barrier homeostasis, mediated by increased endogenous glucocorticoids. Here, we assessed the mechanisms by which PS alters stratum corneum (SC) function. Insomniac psychologic stress (IPS) altered both barrier homeostasis and SC integrity. IPS decreased epidermal cell proliferation, impaired epidermal differentiation, and decreased the density and size of corneodesmosomes (CD), which was linked to degradation of CD proteins (e.g., desmoglein1). Barrier compromise was linked to decreased production and secretion of lamellar bodies (LB), which in turn could be attributed to a decrease in de novo synthesis of epidermal lipids. Topical physiologic lipids (equimolar cholesterol, ceramides, and free fatty acids) normalized both barrier homeostasis and SC integrity in IPS mice, further evidence that lipid deficiency accounted for these functional abnormalities. Thus, PS inhibition of epidermal lipid synthesis results in decreased LB formation and secretion, as well as decreased CD, compromising both permeability barrier homeostasis and SC integrity. These studies suggest that topical treatment with epidermal physiologic lipids could be beneficial in stress-induced, barrier-associated dermatoses, such as psoriasis and atopic dermatitis.