Interleukin-20 promotes angiogenesis in a direct and indirect manner.
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.
Hsieh
M-Y
MY
Chi-Mei Medical Center, Tainan, Taiwan.
Chen
W-Y
WY
Jiang
M-J
MJ
Cheng
B-C
BC
Huang
T-Y
TY
Chang
M-S
MS
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000906:Antibodies / Q000494:pharmacology; D002465:Cell Movement; D049109:Cell Proliferation; D042783:Endothelial Cells / Q000187:drug effects / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D007378:Interleukins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008969:Molecular Sequence Data; D009389:Neovascularization, Pathologic / Q000235:genetics; D018919:Neovascularization, Physiologic / Q000235:genetics; D010766:Phosphorylation; D015398:Signal Transduction; D014158:Transcription, Genetic; D014471:Umbilical Veins / Q000166:cytology; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
D000906:Antibodies; D007378:Interleukins; D042461:Vascular Endothelial Growth Factor A; D016753:Interleukin-10; D020928:Mitogen-Activated Protein Kinases; D020782:Matrix Metalloproteinases; C422042:interleukin 20