Mechanical Stretch Exacerbates Psoriasis by Stimulating Keratinocyte Proliferation and Cytokine Production
Mechanical Stretch Exacerbates Psoriasis by Stimulating Keratinocyte Proliferation and Cytokine Production
复制标题
机械拉伸通过刺激角质形成细胞增殖和细胞因子产生而加剧牛皮癣
DOI：
10.1016/j.jid.2018.12.019
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发表时间：
2019-07-01
影响因子：
6.5
通讯作者：
Wang, Gang
中科院分区：
文献类型：
--
作者：
Qiao, Pei;Guo, Wei;Wang, Gang
牛皮癣是一种慢性炎症性自身免疫性皮肤病，常发生在肘部和膝盖等受到强烈机械拉伸的摩擦部位。然而，机械张力在牛皮癣中的病理作用尚不清楚。在这项研究中，我们研究了角化细胞机械拉伸对牛皮癣临床特征的贡献。我们发现，持续拉伸24小时后，角质细胞增殖和皮肤屏障相关基因表达显著增加。此外，持续拉伸诱导牛皮癣相关的促炎细胞因子、抗菌肽和人原代角化细胞趋化因子的产生。此外，我们通过在BALB/c小鼠背部植入扩张器建立小鼠皮肤扩张模型，在体内评估机械拉伸对表皮的影响。植入扩张器的小鼠表现出明显的表皮增生，皮肤屏障功能受损，表皮角质形成细胞中银屑病相关细胞因子上调。最重要的是，与未植入扩张器的小鼠相比，经咪喹莫特或IL-23治疗的扩张器植入银屑病小鼠的银屑病表型加重。总的来说，我们的研究结果表明，机械拉伸可以通过促进细胞增殖和增加角质形成细胞的促炎细胞因子的产生来加剧银屑病病变。因此，我们的发现为银屑病的发病机制提供了新的见解。
Psoriasis is a chronic inflammatory autoimmune skin disease that often occurs in rubbed areas undergoing a strong mechanical stretch, such as the elbows and knees. However, the pathologic role of mechanical tension in psoriasis remains unclear. In this study, we investigated the contribution of keratinocyte mechanical stretch to the clinical features of psoriasis. We found that keratinocyte proliferation and skin barrier-associated gene expression increased significantly after 24 hours of continuous stretching. Additionally, continuous stretching induced the production of psoriasis-associated proinflammatory cytokines, antibacterial peptides, and chemokines in primary human keratinocytes. Furthermore, we established a murine model of skin expansion by implanting a dilator into the dorsum of BALB/c mice to assess the effect of mechanical stretch on the epidermis in vivo. The dilator-implanted mice displayed prominent epidermal hyperproliferation, impaired skin barrier function, and up-regulation of psoriasis-associated cytokines in epidermal keratinocytes. Most importantly, the dilator-implanted psoriatic mice treated with imiquimod or IL-23 displayed an aggravated psoriatic phenotype compared with mice without dilator implantation. Collectively, our results suggest that mechanical stretch can exacerbate psoriatic lesions by promoting cell proliferation and amplifying the production of proinflammatory cytokines by keratinocytes. Thus, our findings provide new insights into the pathogenesis of psoriasis.