Zhang S-Q, Luo X, Yang S, Liu J-L, Yang C-J, Yin X-Y, Huang H-L, Zhang X-J
Institute of Dermatology & Department of Dermatology at the First Hospital, Anhui Medical University, Hefei, Anhui, China.
Scand J Immunol. 2008 Oct;68(4):397-404. doi: 10.1111/j.1365-3083.2008.02150.x.
Interleukin (IL)-15 is a proinflammatory cytokine and plays a key role in many diseases, including psoriasis. Although its signal transduction pathways in keratinocytes (KC) have been partially elucidated, the effects of IL-15 on expression of IL-15, IL-6 and TNF-alpha in KC are unknown. We have investigated the effects of IL-15 on the expression of the three genes in primary culture of KC by the real-time PCR, Western blot and ELISA. We observed that exogenous IL-15 suppressed the endogenous expression of IL-15, decreased the expression of IL-6 at mRNA and protein levels in KC. The inhibition was blocked by anti-IL-15 monoclonal antibody and by inactive IL-15, I50D mutant IL-15. In contrast, IL-15 increased TNF-alpha transcription in these cells. Mechanistic studies demonstrated that the auto-regulation of IL-15 expression was dependent on activity of ERK1/2 and PI3K. Our studies suggest that there is an auto-inhibitory mechanism controlling cellular IL-15 levels.
白细胞介素（IL）-15是一种促炎细胞因子，在包括银屑病在内的多种疾病中起关键作用。尽管其在角质形成细胞（KC）中的信号转导途径已得到部分阐明，但IL-15对KC中IL-15、IL-6和肿瘤坏死因子-α（TNF-α）表达的影响尚不清楚。我们通过实时定量聚合酶链反应（PCR）、蛋白质免疫印迹法（Western blot）和酶联免疫吸附测定（ELISA）研究了IL-15对原代培养KC中这三个基因表达的影响。我们观察到外源性IL-15抑制了IL-15的内源性表达，降低了KC中IL-6在mRNA和蛋白质水平的表达。这种抑制作用可被抗IL-15单克隆抗体以及无活性的IL-15、I50D突变型IL-15所阻断。相反，IL-15增加了这些细胞中TNF-α的转录。机制研究表明，IL-15表达的自我调节依赖于细胞外信号调节激酶1/2（ERK1/2）和磷脂酰肌醇-3激酶（PI3K）的活性。我们的研究表明，存在一种控制细胞IL-15水平的自我抑制机制。
