Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan.
Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan; Research and Clinical Center for Yusho and Dioxin, Kyushu University Hospital, Fukuoka, 812-8582, Japan; Division of Skin Surface Sensing, Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 812-8582, Japan.
J Dermatol Sci. 2019 Apr;94(1):244-251. doi: 10.1016/j.jdermsci.2019.04.002. Epub 2019 Apr 13.
Scratch injury induces Koebner phenomenon in psoriasis. Smoking is also a risk factor for psoriasis. Keratinocytes can produce various psoriasis-related molecules including TNF, IL1 A, IL1B, IL6, IL12B, IL17C, IL23 A, IL36 A, IL36B, IL36 G, CXCL1, CXCL2, CXCL8, CXCL9, CXCL10, CCL20, IFNB, and CAMP. However, the scratch-induced molecular profiling remains elusive.
To profile the induction pattern of above-mentioned psoriasis-related and keratinocyte-derived molecules by scratch injury in the presence or absence of anti-psoriatic drugs or benzo[a]pyrene, a major environmental pollutant of tobacco smoke.
Confluent normal human keratinocytes were scratched and molecules were assayed by qRT-PCR, ELISA and Western blotting with or without drugs and benzo[a]pyrene.
Among the 18 molecules, the scratch injury on a confluent keratinocyte sheet significantly and selectively upregulated the mRNA expression of four cyto/chemokines, CXCL8, CCL20, IL36G, and TNF, in a scratch-line-number-dependent manner under either low- or high-calcium condition. However, significant protein secretion was only demonstrated for CXCL8 and CCL20. The IL36 G protein was not secreted, but its intracellular level was significantly upregulated by scratch injury, whereas neither the secretion nor the intracellular level of TNF protein was affected by scratch injury. Dexamethasone, but not maxacalcitol nor the phosphodiesterase 4 inhibitor apremilast, partially inhibited the CXCL8 and CCL20 secretion. Benzo[a]pyrene significantly and synergistically enhanced the scratch-induced CCL20 secretion that may explain why smoking is a risk factor for psoriasis.
CCL20 and to a less extent CXCL8 may play a key role in triggering the Koebner phenomenon after scratch injury to keratinocytes.
划痕损伤可诱发银屑病的同形反应。吸烟也是银屑病的一个危险因素。角质形成细胞可产生多种与银屑病相关的分子，包括 TNF、IL1A、IL1B、IL6、IL12B、IL17C、IL23A、IL36A、IL36B、IL36G、CXCL1、CXCL2、CXCL8、CXCL9、CXCL10、CCL20、IFNB 和 CAMP。然而，划痕诱导的分子谱仍然难以捉摸。
在存在或不存在抗银屑病药物或苯并[a]芘（烟草烟雾中主要的环境污染物）的情况下，通过划痕损伤来描绘上述与银屑病相关和角质形成细胞衍生的分子的诱导模式。
用 qRT-PCR、ELISA 和 Western blot 法检测划痕损伤后有无药物和苯并[a]芘存在时，在汇合的正常人角质形成细胞上这些分子的表达。
在 18 种分子中，在低钙或高钙条件下，在汇合的角质形成细胞单层上划痕，以划痕线数量依赖的方式显著且选择性地上调了 4 种细胞因子/趋化因子（CXCL8、CCL20、IL36G 和 TNF）的 mRNA 表达。然而，只有 CXCL8 和 CCL20 有显著的蛋白分泌。IL36G 蛋白没有分泌，但划痕损伤显著上调了其细胞内水平，而 TNF 蛋白的分泌和细胞内水平均不受划痕损伤的影响。地塞米松，但不是卡泊三醇或磷酸二酯酶 4 抑制剂阿普司特，部分抑制了 CXCL8 和 CCL20 的分泌。苯并[a]芘显著且协同增强了划痕诱导的 CCL20 分泌，这可能解释了为什么吸烟是银屑病的一个危险因素。
CCL20 和在较小程度上的 CXCL8 可能在角质形成细胞划痕损伤后触发同形反应中起关键作用。
