Eccrine sweat contains IL-1α, IL-1β and IL-31 and activates epidermal keratinocytes as a danger signal.
Eccrine sweat contains IL-1α, IL-1β and IL-31 and activates epidermal keratinocytes as a danger signal.
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DOI：
10.1371/journal.pone.0067666
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Sayama K
中科院分区：
文献类型：
--
作者：
Dai X;Okazaki H;Hanakawa Y;Murakami M;Tohyama M;Shirakata Y;Sayama K
外泌汗液分泌到皮肤表面，对正常皮肤无害，但可加重特应性皮炎的湿疹性病变。虽然外泌汗液含有大量矿物质，蛋白质和蛋白水解酶，但它如何引起皮肤炎症尚不清楚。我们假设它直接刺激角质形成细胞，作为一个危险信号。运动后从健康志愿者的手臂收集外分泌汗液，并通过ELISA定量汗液中促炎细胞因子的水平。我们在汗液样本中检测到IL-1α、IL-1β和高水平IL-31的存在。为了研究汗液是否激活角质形成细胞，用浓缩汗液刺激正常人角质形成细胞。Western blot分析证实了汗液刺激的角质形成细胞中NF-κB、ERK和JNK信号的激活。使用总RNA的实时PCR和上清液的ELISA分析显示汗液上调IL-8和IL-1β。此外，用IL-1 R拮抗剂预处理阻断汗液刺激的细胞因子产生和信号激活，表明生物活性IL-1是汗液激活角质形成细胞的主要因素。此外，IL-31似乎是另一种汗液刺激物，其激活角质形成细胞以产生炎性细胞因子CCL 2。汗液分泌到皮肤表面，不与正常皮肤中的角质形成细胞接触。然而，在具有缺陷的皮肤屏障的皮肤中，例如受特应性皮炎影响的皮肤，汗液细胞因子可直接作用于表皮角质形成细胞，导致其活化。总之，外泌汗液含有促炎细胞因子IL-1和IL-31，并激活表皮角质形成细胞作为危险信号。
Eccrine sweat is secreted onto the skin's surface and is not harmful to normal skin, but can exacerbate eczematous lesions in atopic dermatitis. Although eccrine sweat contains a number of minerals, proteins, and proteolytic enzymes, how it causes skin inflammation is not clear. We hypothesized that it stimulates keratinocytes directly, as a danger signal. Eccrine sweat was collected from the arms of healthy volunteers after exercise, and levels of proinflammatory cytokines in the sweat were quantified by ELISA. We detected the presence of IL-1α, IL-1β, and high levels of IL-31 in sweat samples. To investigate whether sweat activates keratinocytes, normal human keratinocytes were stimulated with concentrated sweat. Western blot analysis demonstrated the activation of NF-κB, ERK, and JNK signaling in sweat-stimulated keratinocytes. Real-time PCR using total RNA and ELISA analysis of supernatants showed the upregulation of IL-8 and IL-1β by sweat. Furthermore, pretreatment with IL-1R antagonist blocked sweat-stimulated cytokine production and signal activation, indicating that bioactive IL-1 is a major factor in the activation of keratinocytes by sweat. Moreover, IL-31 seems to be another sweat stimulator that activates keratinocytes to produce inflammatory cytokine, CCL2. Sweat is secreted onto the skin's surface and does not come into contact with keratinocytes in normal skin. However, in skin with a defective cutaneous barrier, such as atopic dermatitis-affected skin, sweat cytokines can directly act on epidermal keratinocytes, resulting in their activation. In conclusion, eccrine sweat contains proinflammatory cytokines, IL-1 and IL-31, and activates epidermal keratinocytes as a danger signal.
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