【Aim】
The role of tumor necrosis factor (TNF)-α in angiogenesis was first reported in 1987 in a rat corneal model, but the exact mechanism is not fully understood. In this study, we investigated the mechanism of TNFα-induced tube formation in human endothelial cells.
【Method】
The mechanism of TNFα-induced tube formation was analyzed by the Matrigel assay using the human vascular endothelial cell line EA.hy926. To examine the effects of TNFα, vascular endothelial cells were stained with calcein-AM and observed under a microscope. Various gene expression levels were determined by real-time PCR, flow cytometry (FACS), and Western blot (WB). In addition, RNAi experiments were performed to investigate the involvement of integrin.
【Result】
TNFα induced endothelial tube formation in a dose-dependent manner. TNFα also significantly upregulated integrin α3 and β8 at both mRNA and protein levels, whereas other integrin subunits, vascular endothelial growth factor (VEGF), and matrix metalloproteinases (MMP-2 and MMP-9) were not altered at the mRNA level. In addition, TNFα-induced tube formation was effectively blocked by integrin α3 and β8 RNAi. 
【Conclusion】
Our results suggest that TNFα promotes tube formation of vascular endothelial cells through integrin α3/β8, and RNAi of α3/β8 may be an inhibitor of TNFα-induced angiogenesis, and integrin α3/β8 may be a potential target for TNFα-induced angiogenic diseases.