IL-22/STAT3-Induced Increases in SLURP1 Expression within Psoriatic Lesions Exerts Antimicrobial Effects against Staphylococcus aureus.
IL-22/STAT3-Induced Increases in SLURP1 Expression within Psoriatic Lesions Exerts Antimicrobial Effects against Staphylococcus aureus.
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DOI：
10.1371/journal.pone.0140750
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Misawa H
中科院分区：
文献类型：
--
作者：
Moriwaki Y;Takada K;Nagasaki T;Kubo N;Ishii T;Kose K;Kageyama T;Tsuji S;Kawashima K;Misawa H
SLURP1是一种常染色体隐性遗传病（MDM）的致病基因，MDM是一种以弥漫性掌跖角化病和侵袭性角化病为特征的皮肤病。此外，虽然SLURP1可能是角质形成细胞中重要的增殖/分化因子，但SLURP1与银屑病、特应性皮炎等其他皮肤疾病之间的可能关系尚未研究，SLURP1在角质形成细胞中表达的病理生理控制在很大程度上是未知的。我们的目的是通过咪喹莫特（IMQ）诱导的银屑病模型小鼠和正常人表皮角质形成细胞（NHEKs）来研究SLURP1在银屑病病理生理中的作用。SLURP1在imq诱导的银屑病模型小鼠皮肤中表达上调。在炎症因子IL-17、IL-22和TNF-α刺激的NHEKs中，SLURP1 mRNA的表达被IL-22而非其他两种细胞因子显著上调。在STAT3抑制剂处理或靶向STAT3的siRNA转染的NHEKs中，IL-22的刺激作用完全被抑制。由于IL-22诱导上皮细胞中抗菌蛋白的产生，我们评估了SLURP1对金黄色葡萄球菌（S. aureus）的抗菌活性，已知金黄色葡萄球菌与银屑病的疾病严重程度相关。SLURP1显著抑制金黄色葡萄球菌的生长。这些结果表明，SLURP1通过调节角质细胞的增殖和分化，抑制金黄色葡萄球菌的生长，参与银屑病的病理生理。
SLURP1 is the causal gene for Mal de Meleda (MDM), an autosomal recessive skin disorder characterized by diffuse palmoplantar keratoderma and transgressive keratosis. Moreover, although SLURP1 likely serves as an important proliferation/differentiation factor in keratinocytes, the possible relation between SLURP1 and other skin diseases, such as psoriasis and atopic dermatitis, has not been studied, and the pathophysiological control of SLURP1 expression in keratinocytes is largely unknown. Our aim was to examine the involvement of SLURP1 in the pathophysiology of psoriasis using an imiquimod (IMQ)-induced psoriasis model mice and normal human epidermal keratinocytes (NHEKs). SLURP1 expression was up-regulated in the skin of IMQ-induced psoriasis model mice. In NHEKs stimulated with the inflammatory cytokines IL-17, IL-22 and TNF-α, which are reportedly expressed in psoriatic lesions, SLURP1 mRNA expression was significantly up-regulated by IL-22 but not the other two cytokines. The stimulatory effect of IL-22 was completely suppressed in NHEKs treated with a STAT3 inhibitor or transfected with siRNA targeting STAT3. Because IL-22 induces production of antimicrobial proteins in epithelial cells, the antibacterial activity of SLURP1 was assessed against Staphylococcus aureus (S. aureus), which is known to be associated with disease severity in psoriasis. SLURP1 significantly suppressed the growth of S. aureus. These results indicate SLURP1 participates in pathophysiology of psoriasis by regulating keratinocyte proliferation and differentiation, and by suppressing the growth of S. aureus.