Mechanism of UVB-Induced Wrinkling of the Skin: Paracrine Cytokine Linkage between Keratinocytes and Fibroblasts Leading to the Stimulation of Elastase
Mechanism of UVB-Induced Wrinkling of the Skin: Paracrine Cytokine Linkage between Keratinocytes and Fibroblasts Leading to the Stimulation of Elastase
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DOI：
10.1038/jidsymp.2009.11
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发表时间：
2009-08-01
影响因子：
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通讯作者：
Imokawa, Genji
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文献类型：
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作者：
Imokawa, Genji
在临床研究中，面部皱纹的形成与皮肤弹性的丧失密切相关。用UVB辐射以皮下剂量重复照射动物皮肤会显著降低其弹性，导致皱纹的形成。重复的UVB照射导致弹性纤维的三维结构发生显著改变，这与随后皮肤弹性性能的降低密切相关。虽然UVB照射刺激真皮中成纤维细胞弹性蛋白酶的活性，但合成的成纤维细胞弹性蛋白酶特异性抑制剂可防止皱纹形成。不同浓度的弹性蛋白酶抑制剂（R-2>0.9）的作用揭示了皱纹形成、弹性性能和弹性纤维线性之间的密切相互关系，这表明皮肤成纤维细胞增强的弹性蛋白酶活性在UVB照射机制中起着关键作用。在体外研究中，我们确定了角质形成细胞和成纤维细胞之间的旁分泌联系，通过成纤维细胞弹性蛋白酶的上调导致皱纹形成。这些研究支持我们的假说皱纹形成的机制，细胞因子的表达被激活的表皮角质形成细胞的UVB辐射，并触发真皮成纤维细胞，以增加他们的弹性蛋白酶的表达。
In clinical studies, the formation of facial wrinkles has been closely linked to the loss of elastic properties of the skin. Repetitive irradiation of animal skin with UVB radiation at suberythemal doses significantly reduces its elastic properties, resulting in the formation of wrinkles. Repetitive UVB irradiation elicits a marked alteration in the three-dimensional structure of elastic fibers, which is closely associated with a subsequent reduction in the elastic properties of the skin. Although UVB irradiation stimulates the activity of fibroblast elastases in the dermis, a synthetic inhibitor specific for fibroblast elastases prevents wrinkle formation. The close interrelationships among wrinkle formation, elastic properties, and elastic fiber linearity are revealed by the effects of different concentrations of the elastase inhibitor (R-2>0.9), suggesting that enhanced elastase activity by dermal fibroblasts plays a pivotal role in the UVB wrinkling mechanism. In in vitro studies we identified a paracrine linkage between keratinocytes and fibroblasts that leads to wrinkle formation through the upregulation of fibroblast elastases. These studies support our hypothesis for a mechanism of wrinkle formation by which cytokine expression is activated in epidermal keratinocytes by UVB radiation and triggers dermal fibroblasts to increase their expression of elastase.