IL-17 and IL-22 mediate IL-20 subfamily cytokine production in cultured keratinocytes via increased IL-22 receptor expression
IL-17 and IL-22 mediate IL-20 subfamily cytokine production in cultured keratinocytes via increased IL-22 receptor expression
复制标题
DOI：
10.1002/eji.200939473
复制
发表时间：
2009-10-01
影响因子：
5.4
通讯作者：
Hashimoto, Koji
中科院分区：
文献类型：
--
作者：
Tohyama, Mikiko;Hanakawa, Yasushi;Hashimoto, Koji
IL-20细胞因子亚家族成员包括IL-19、IL-20和IL-24在银屑病皮损中高表达。在这里，我们证明了银屑病介质IL-17和IL-22协同诱导培养的人角质形成细胞产生IL-20亚家族蛋白。有趣的是，与正常皮肤相比，表皮病变中IL-22受体(IL-22R)的表达也增加。用腺病毒载体模拟银屑病条件下培养的角质形成细胞过度表达IL-22R显著增强IL-17和IL-22诱导的IL-20亚家族细胞因子的产生。此外，IL-17和IL-22协同促进MIP-3α、IL-8和肝素结合的EGF样生长因子(HB-EGF)的产生，这取决于IL-22R的表达量。此外，由于IL-20和IL-24与IL-22共享IL-22R，因此IL-20和IL-24的功能也增强了。IL-20和IL-24的作用与IL-22相似，IL-24的表达强于IL-20。IL-24和IL-17的组合增加了MIP-3α、IL-8和HB-EGF的产生，IL-22和IL-17的组合也是如此。这些数据表明，表皮角质形成细胞中IL-22R的表达增加，通过增强IL-22和IL-17的协同作用，诱导IL-20亚家族、趋化因子和生长因子的产生，参与了银屑病的发病。
IL-20 cytokine subfamily members, including IL-19, IL-20, and IL-24, are highly expressed in psoriatic skin lesions. Here, we demonstrate that psoriasis mediators IL-17 and IL-22 synergistically induce the production of IL-20 subfamily proteins in cultured human keratinocytes. interestingly, expression of the IL-22 receptor (IL-22R) also increased in epidermal lesions versus normal skin. IL-22R over-expression using an adenoviral vector to mimic psoriatic conditions in cultured keratinocytes significantly enhanced IL-17- and IL-22-induced production of IL-20 subfamily cytokines. Furthermore, IL-17 and IL-22 coordinately enhanced MIP-3 alpha, IL-8, and heparin-binding EGF-like growth factor (HB-EGF) production, depending on the amount of IL-22R expression. Additionally, because IL-20 and IL-24 share the IL-22R with IL-22, the function of IL-20 and IL-24 was also increased. IL-20 and IL-24 have effects similar to that of IL-22; IL-24 showed more potent expression than IL-20. A combination of IL-24 and IL-17 increased the production of MIP-3 alpha, IL-8, and HB-EGF, as did a combination of IL-22 and IL-17. These data indicate that increased IL-22R expression in epidermal keratinocytes contributes to the pathogenesis of psoriasis through enhancing the coordinated effects of IL-22 and IL-17, inducing the production of the IL-20 subfamily, chemokines, and growth factors.