Interleukin-20 promotes angiogenesis in a direct and indirect manner
Interleukin-20 promotes angiogenesis in a direct and indirect manner
复制标题
DOI：
10.1038/sj.gene.6364291
复制
发表时间：
2006-04-01
影响因子：
5
通讯作者：
Chang, MS
中科院分区：
文献类型：
--
作者：
Hsieh, MY;Chen, WY;Chang, MS
IL-20属于IL-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。为了探讨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），分析其对内皮细胞的作用。IL-20可诱导内皮细胞增殖，其活性可被抗人IL-20单克隆抗体和可溶性IL-20受体（R）1和sIL-20 R2特异性阻断。IL-20的可变剪接变体被分离，并且也显示出诱导HUVEC和HMEC的增殖。用IL-10和IL-20两者处理HUVEC证明IL-10拮抗IL-20的活性，因为它减少了IL-20诱导的HUVEC增殖。IL-20可显著诱导HUVECs在Matrigel上的迁移和血管形成。在体内，IL-20还增强肿瘤血管生成。IL-20与HUVECs孵育诱导bFGF、VEGF、MMP-2、MMP-9和IL-8的转录。此外，HUVEC与IL-20孵育诱导ERK 1/2、p38和JNK的磷酸化。因此，IL-20是一种多效性细胞因子并促进血管生成。
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.