Department of Dermatology, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan.
J Dermatol Sci. 2013 Aug;71(2):107-14. doi: 10.1016/j.jdermsci.2013.04.014. Epub 2013 Apr 19.
Interleukin (IL)-33 is a dual functional, IL-1 family member cytokine, whose exact roles in inflammatory skin diseases are still unknown. IL-17A is a key cytokine in the pathogenesis of psoriasis.
We investigated if IL-17A could induce IL-33 in epidermal keratinocytes, and the signaling mechanisms involved.
IL-33 levels were evaluated by RT-PCR and western blot in human keratinocytes following IL-17A simulation. IL-33 immunohistochemical staining of psoriatic skin samples was also performed and compared with that of control tissues. The role of signaling pathways downstream of IL-17A was investigated using small molecule inhibitors of EGFR, ERK, p38, and JAK. Adenovirus vector expressing dominant negative STAT1 was also utilized.
IL-33 and its receptor, ST2L, were expressed in the psoriatic epidermis, and the associated infiltrating cells. IL-17A induced IL-33 expression at mRNA and protein levels in a time- and concentration-dependent manner. IL-17A caused phosphorylation of EGFR, ERK, p38, and STAT1. IL-17A-induced IL-33 expression was blocked by the addition of EGFR, ERK, p38, and JAK inhibitors, and dominant negative STAT1-expressing adenovirus vector.
IL-17A induced IL-33 in NHEKs through EGFR, ERK, p38, and JAK/STAT1 pathways, which were necessary for the induction of IL-33. IL-33, induced by IL-17A in epidermal keratinocytes, may be involved in the pathophysiology of inflammatory skin diseases, including psoriasis.
白细胞介素 (IL)-33 是一种双功能的 IL-1 家族细胞因子，其在炎症性皮肤病中的确切作用仍不清楚。IL-17A 是银屑病发病机制中的关键细胞因子。
我们研究了 IL-17A 是否可以诱导表皮角质形成细胞产生 IL-33，以及涉及的信号机制。
用 IL-17A 模拟后，通过 RT-PCR 和 Western blot 评估人角质形成细胞中 IL-33 的水平。还对银屑病皮肤样本进行了 IL-33 免疫组织化学染色，并与对照组织进行了比较。使用 EGFR、ERK、p38 和 JAK 的小分子抑制剂以及表达显性负 STAT1 的腺病毒载体来研究 IL-17A 下游信号通路的作用。
IL-33 和其受体 ST2L 在银屑病表皮及其相关浸润细胞中表达。IL-17A 以时间和浓度依赖的方式诱导 IL-33 在 mRNA 和蛋白水平上的表达。IL-17A 引起 EGFR、ERK、p38 和 STAT1 的磷酸化。加入 EGFR、ERK、p38 和 JAK 抑制剂以及表达显性负 STAT1 的腺病毒载体可阻断 IL-17A 诱导的 IL-33 表达。
IL-17A 通过 EGFR、ERK、p38 和 JAK/STAT1 途径诱导 NHEKs 中的 IL-33，这些途径对于诱导 IL-33 是必要的。IL-17A 在表皮角质形成细胞中诱导的 IL-33 可能参与包括银屑病在内的炎症性皮肤病的病理生理学。
