This article explores the role of interleukin-6 (IL-6) in inducing vascular endothelial growth factor (VEGF) expression, a key factor in angiogenesis. The study demonstrates that IL-6 treatment significantly increases VEGF mRNA levels in various cell lines, with an induction level comparable to that of hypoxia or cobalt chloride, which are known to induce VEGF. The effect of IL-6 on VEGF expression is mediated through both DNA elements in the promoter region and specific motifs in the 5′-untranslated region (5′-UTR) of VEGF mRNA. The 5′-UTR of VEGF is exceptionally long (1038 base pairs) and rich in G + C, suggesting that secondary structures within this region may play a crucial role in VEGF expression through both transcriptional and post-transcriptional control mechanisms. The study also shows that IL-6 may induce angiogenesis indirectly by upregulating VEGF expression. VEGF is a potent angiogenic agent that acts as a specific mitogen for vascular endothelial cells. The promoter region of VEGF contains numerous putative binding sites for various transcription factors, and the 5′-UTR is also rich in DNA binding motifs. VEGF is expressed in normal tissues and during physiological conditions such as wound healing and embryo development, and its expression is also observed during abnormal conditions like tumor angiogenesis. The study used transient transfection assays to demonstrate that IL-6 induces VEGF expression through specific DNA elements in the promoter region and the 5′-UTR. Deletions in these regions were shown to affect the responsiveness of VEGF to IL-6 and cobalt. The results suggest that the 5′-UTR plays an essential role in VEGF expression and that DNA motifs in this region may work synergistically with those in the promoter region. The findings highlight the importance of the 5′-UTR in VEGF expression and suggest that both transcriptional and post-transcriptional control mechanisms are involved. The study also indicates that IL-6 may act as an indirect angiogenic factor by inducing VEGF expression, and that other cytokines such as IFN-β and TNF-α can also induce VEGF expression. These findings contribute to a better understanding of the molecular mechanisms underlying VEGF expression and angiogenesis.This article explores the role of interleukin-6 (IL-6) in inducing vascular endothelial growth factor (VEGF) expression, a key factor in angiogenesis. The study demonstrates that IL-6 treatment significantly increases VEGF mRNA levels in various cell lines, with an induction level comparable to that of hypoxia or cobalt chloride, which are known to induce VEGF. The effect of IL-6 on VEGF expression is mediated through both DNA elements in the promoter region and specific motifs in the 5′-untranslated region (5′-UTR) of VEGF mRNA. The 5′-UTR of VEGF is exceptionally long (1038 base pairs) and rich in G + C, suggesting that secondary structures within this region may play a crucial role in VEGF expression through both transcriptional and post-transcriptional control mechanisms. The study also shows that IL-6 may induce angiogenesis indirectly by upregulating VEGF expression. VEGF is a potent angiogenic agent that acts as a specific mitogen for vascular endothelial cells. The promoter region of VEGF contains numerous putative binding sites for various transcription factors, and the 5′-UTR is also rich in DNA binding motifs. VEGF is expressed in normal tissues and during physiological conditions such as wound healing and embryo development, and its expression is also observed during abnormal conditions like tumor angiogenesis. The study used transient transfection assays to demonstrate that IL-6 induces VEGF expression through specific DNA elements in the promoter region and the 5′-UTR. Deletions in these regions were shown to affect the responsiveness of VEGF to IL-6 and cobalt. The results suggest that the 5′-UTR plays an essential role in VEGF expression and that DNA motifs in this region may work synergistically with those in the promoter region. The findings highlight the importance of the 5′-UTR in VEGF expression and suggest that both transcriptional and post-transcriptional control mechanisms are involved. The study also indicates that IL-6 may act as an indirect angiogenic factor by inducing VEGF expression, and that other cytokines such as IFN-β and TNF-α can also induce VEGF expression. These findings contribute to a better understanding of the molecular mechanisms underlying VEGF expression and angiogenesis.