Involvement of interleukin-8, vascular endothelial growth factor, and basic fibroblast growth factor in tumor necrosis factor alpha-dependent angiogenesis.

摘要: Tumor necrosis factor alpha (TNF-alpha) is a macrophage/monocyte-derived polypeptide which modulates the expression of various genes in vascular endothelial cells and induces angiogenesis. However, underlying mechanism by TNF-alpha mediates angiogenesis not completely understood. In this study, we assessed whether TNF-alpha-induced mediated through itself or indirectly other angiogenesis-promoting factors. Cellular mRNA levels interleukin-8 (IL-8), growth (VEGF), basic fibroblast (bFGF), their receptors were increased after treatment human microvascular with (100 U/ml). TNF-alpha-dependent tubular morphogenesis was inhibited administration anti-IL-8, anti-VEGF, anti-bFGF antibodies, coadministration all three antibodies almost abrogated formation. Moreover, Sp1, NF-kappaB, c-Jun antisense oligonucleotides cells. Administration NF-kappaB oligonucleotide IL-8 production partially VEGF production, an Sp1 sequence VEGF. A significantly bFGF but did affect anti-IL-8 anti-VEGF antibody also blocked neovascularization rabbit cornea vivo. Thus, appears to be modulated angiogenic factors, both vitro vivo, pathway controlled paracrine and/or autocrine mechanisms.