PERTURBATION OF EPIDERMAL BARRIER FUNCTION CORRELATES WITH INITIATION OF CYTOKINE CASCADE IN HUMAN SKIN
PERTURBATION OF EPIDERMAL BARRIER FUNCTION CORRELATES WITH INITIATION OF CYTOKINE CASCADE IN HUMAN SKIN
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DOI：
10.1016/s0190-9622(94)70059-1
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发表时间：
1994-04-01
影响因子：
13.8
通讯作者：
NAIDU, Y
中科院分区：
文献类型：
--
作者：
NICKOLOFF, BJ;NAIDU, Y
背景：皮肤的一个重要功能是作为屏障，从而提供保护免受外部环境的影响。表皮角质形成细胞通过产生完整的角质层来建立这种屏障。在过去，角质形成细胞只被赞赏这种相当惰性，被动的结构责任，而不是他们的潜在的动态贡献炎症或免疫介导的反应。目的：我们的目的是检查当人类皮肤的屏障功能被反复的胶带剥离废除时发生的分子和细胞事件的级联，其物理地去除角质层而不对下面的表皮角质形成细胞诱导任何细胞病变效应。8名健康志愿者反复进行胶带剥离，并对胶带剥离后1至24小时内获得的皮肤连续穿孔活检标本进行分析通过对冷冻切片进行免疫染色来检测蛋白抗原。结果：反复胶带剥离后，角质形成细胞在数小时内就被激活。反应包括上调角蛋白-16表达和角质形成细胞增殖，伴随着表皮和真皮隔室中细胞因子和粘附分子mRNA和蛋白质的特定概况的产生。从皮肤表皮部分分离的RNA种类的聚合酶链反应扩增显示，胶带剥离后6小时，编码肿瘤坏死因子-α、IL-8、IL-10、干扰素γ、细胞间粘附分子-1、转化生长因子-α和转化生长因子-β的mRNA增加。在皮肤样本中，肿瘤坏死因子-α、IL-8、IL-10或转化生长因子-α mRNA没有增加。免疫染色显示，角质形成细胞细胞间粘附分子-1增加剥离后6小时，并伴随着内皮细胞表达的E-选择素（内皮细胞粘附分子-1）和血管细胞粘附分子-1。在胶带剥离皮肤中6小时后发生的这些分子事件先于炎性细胞从循环进入真皮或表皮的任何运动，因此反映了正常人皮肤固有细胞中发生的变化。这些变化都没有发生在人谁经历了有限的磁带剥离没有屏障disturbance.Conclusion：结果突出的快速和独特的反应表皮角质形成细胞，并证明这些细胞可以积极参与一个更大的数量比生产的表皮屏障以外的稳态反应。
Background: An important function of skin is to serve as a barrier and thus provide protection from the external environment. The epidermal keratinocyte establishes this barrier by producing an intact stratum corneum. In the past, keratinocytes were appreciated only for this rather inert, passive structural responsibility and not for their potential dynamic contribution to inflammatory or immune-mediated reactions.Objective: Our purpose was to examine the cascade of molecular and cellular events that occur when the barrier function of human skin is abrogated by repeated tape stripping, which physically removes the stratum corneum without inducing any cytopathic effects on the underlying epidermal keratinocytes.Methods: Eight healthy human volunteers underwent repeated tape stripping and sequential punch biopsy specimens of skin obtained between 1 and 24 hours after tape stripping were analyzed for protein antigens by immunostaining of cryostat-cut sections. The presence or absence of various messenger RNAs (mRNAs) were detected by polymerase chain reaction.Results: After repeated tape stripping, keratinocytes became activated within hours. The responses included up-regulation of keratin-16 expression and keratinocyte proliferation accompanied by production of a specific profile of cytokine and adhesion molecule mRNAs and proteins in both epidermal and dermal compartments. Polymerase chain reaction amplification of RNA species isolated from the epidermal portion of skin revealed increases 6 hours after tape stripping in mRNA coding for tumor necrosis factor-alpha; IL-8, IL-10, interferon gamma, intercellular adhesion molecule-1, transforming growth factor-alpha, and transforming growth factor-beta. There was no increase in tumor necrosis factor-alpha, IL-8, IL-10, or transforming growth factor-alpha mRNAs in the dermal samples. Immunostaining revealed that keratinocyte intercellular adhesion molecule-1 was increased 6 hours after stripping and was accompanied by endothelial cell expression of E-selectin (endothelial cell adhesion molecule-1) and vascular cell adhesion molecule-1. These molecular events, which occurred after 6 hours in tape-stripped skin, preceded any movement of inflammatory cells from the circulation into dermis or epidermis and hence reflect changes that occur in cells indigenous to normal human skin. None of these changes occurred in persons who underwent limited tape strippings without barrier perturbation.Conclusion: The results highlight the rapid and distinctive responses of epidermal keratinocytes and demonstrate that these cells can actively participate in a far greater number of homeostatic responses other than the production of the epidermal barrier.