Mohamadzadeh M, Takashima A, Dougherty I, Knop J, Bergstresser P R, Cruz P D
Department of Dermatology, University of Mainz, Germany.
J Immunol. 1995 Nov 1;155(9):4492-6.
Ultraviolet B (UVB) radiation is a potent modulator of skin-related immune responses, particularly those involving the synthesis and the secretion of cytokines. The discovery of a new T cell mitogen, IL-15, prompted use to investigate its expression in skin and to examine the effects of UVB radiation on such expression. RNA from unirradiated and UVB-irradiated epidermal and dermal sheets derived from human foreskin as well as from unirradiated and UVB-irradiated skin cell populations were assayed for IL-15 expression by semiquantitative RT-PCR. Constitutive levels of IL-15 mRNA were detected in dermal sheets, but not in epidermal sheets. Following UVB treatment, IL-15 mRNA was induced in epidermal sheets and enhanced in dermal sheets. UVB-inducible epidermal expression of IL-15 mRNA was traced to HLA-DR- cells (presumably keratinocytes) and not to HLA-DR+ cells (Langerhans cells). Cultured keratinocytes and dermal fibroblasts displayed basal levels of IL-15 mRNA that were also up-regulated following UVB exposure. Immunoblot analysis revealed secretion of IL-15 protein by keratinocytes that was enhanced following UVB treatment. These results constitute the first report of IL-15 mRNA expression and protein production in human skin. In addition to expanding the known influence of UVB radiation on the capacity of keratinocytes and dermal fibroblasts to express immunomodulatory cytokines, these findings suggest a new mechanism by which UVB can promote Ag-independent T cell responses via elaboration of IL-15.
紫外线B(UVB)辐射是皮肤相关免疫反应的有力调节因子,尤其是那些涉及细胞因子合成和分泌的反应。一种新的T细胞有丝分裂原白细胞介素-15(IL-15)的发现促使我们研究其在皮肤中的表达,并检测UVB辐射对这种表达的影响。通过半定量逆转录聚合酶链反应(RT-PCR)检测来自人包皮的未照射和UVB照射的表皮和真皮片以及未照射和UVB照射的皮肤细胞群体中的RNA的IL-15表达。在真皮片中检测到IL-15 mRNA的组成水平,但在表皮片中未检测到。UVB处理后,表皮片中诱导出IL-15 mRNA,真皮片中则增强。UVB诱导的表皮IL-15 mRNA表达可追溯到HLA-DR-细胞(可能是角质形成细胞),而不是HLA-DR+细胞(朗格汉斯细胞)。培养的角质形成细胞和真皮成纤维细胞显示出IL-15 mRNA的基础水平,UVB照射后也上调。免疫印迹分析显示角质形成细胞分泌IL-15蛋白,UVB处理后增强。这些结果构成了关于人皮肤中IL-15 mRNA表达和蛋白产生的首次报道。除了扩大UVB辐射对角质形成细胞和真皮成纤维细胞表达免疫调节细胞因子能力的已知影响外,这些发现还提示了一种新机制,通过该机制UVB可通过释放IL-15促进不依赖抗原的T细胞反应。