Hsieh M-Y, Chen W-Y, Jiang M-J, Cheng B-C, Huang T-Y, Chang M-S
Chi-Mei Medical Center, Tainan, Taiwan.
Genes Immun. 2006 Apr;7(3):234-42. doi: 10.1038/sj.gene.6364291.
IL-20 belongs to the IL-10 family and is involved in the pathogenesis of keratinocyte hyperproliferation in vivo. Endothelial cells express IL-20 receptors. To explore the function of IL-20 on endothelial cells, we treated human umbilical vein endothelial cells (HUVECs) and human microvascular endothelial cells (HMECs) with human IL-20 and analyzed its effect on endothelial cells. IL-20 induced proliferation of endothelial cells and the activity was specifically blocked by anti-human-IL-20 monoclonal antibody and soluble (s)IL-20 receptor (R)1 and sIL-20R2. An alternatively spliced variant of IL-20 was isolated and also was shown to induce proliferation of HUVECs and HMECs. Treatment of HUVECs with both IL-10 and IL-20 demonstrated that IL-10 antagonized the activity of IL-20 because it diminished IL-20-induced proliferation of HUVECs. IL-20 significantly induced HUVECs migration and vascular tube formation on Matrigel in vitro. In vivo, IL-20 also enhanced tumor angiogenesis. Incubation of IL-20 with HUVECs induced transcripts of bFGF, VEGF, MMP-2, MMP-9, and IL-8. Furthermore, incubation of HUVECs with IL-20 induced phosphorylation of ERK1/2, p38, and JNK. Thus, IL-20 is a pleiotropic cytokine and promotes angiogenesis.
白细胞介素-20（IL-20）属于白细胞介素-10家族，参与体内角质形成细胞过度增殖的发病机制。内皮细胞表达IL-20受体。为了探究IL-20对内皮细胞的作用，我们用人IL-20处理人脐静脉内皮细胞（HUVECs）和人微血管内皮细胞（HMECs），并分析其对内皮细胞的影响。IL-20诱导内皮细胞增殖，且该活性被抗人IL-20单克隆抗体以及可溶性（s）IL-20受体（R）1和sIL-20R2特异性阻断。分离出一种IL-20的可变剪接变体，其也显示可诱导HUVECs和HMECs增殖。用IL-10和IL-20共同处理HUVECs表明，IL-10拮抗IL-20的活性，因为它减少了IL-20诱导的HUVECs增殖。IL-20在体外显著诱导HUVECs迁移以及在基质胶上形成血管管。在体内，IL-20也增强肿瘤血管生成。IL-20与HUVECs孵育可诱导碱性成纤维细胞生长因子（bFGF）、血管内皮生长因子（VEGF）、基质金属蛋白酶-2（MMP-2）、基质金属蛋白酶-9（MMP-9）和白细胞介素-8（IL-8）的转录本。此外，IL-20与HUVECs孵育可诱导细胞外信号调节激酶1/2（ERK1/2）、p38和应激活化蛋白激酶（JNK）的磷酸化。因此，IL-20是一种多效性细胞因子，可促进血管生成。
