Interleukin-6 (IL-6) induces vascular endothelial growth factor (VEGF) expression. This study demonstrates that treatment of various cell lines with IL-6 for 6–48 hours significantly induces VEGF mRNA, comparable to hypoxia or cobalt chloride. The effect of IL-6 is mediated by 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 it plays a role in VEGF expression through transcriptional and post-transcriptional control mechanisms. VEGF is a potent angiogenic agent that acts as a mitogen for vascular endothelial cells. It is encoded by a single gene and produces four isoforms through alternative splicing. The 165-amino acid isoform is the most abundant. VEGF expression is regulated by various factors, including hypoxia, cytokines, and growth factors. The study shows that IL-6 induces VEGF expression, which may promote angiogenesis indirectly. The 5'-UTR of VEGF is essential for its expression and contains DNA motifs that work cooperatively with promoter elements. The results suggest that IL-6 should be considered an indirect inducer of angiogenesis through VEGF expression. The study also shows that other cytokines, such as IFN-β and TNF-α, can induce VEGF expression. The 5'-UTR of VEGF is important for its expression and may be involved in translational regulation. The study provides evidence that IL-6 induces VEGF expression through specific DNA motifs in the promoter and 5'-UTR regions. The results indicate that the secondary structure of the 5'-UTR may be important for efficient VEGF expression and suggest that transcription and post-transcriptional control mechanisms are involved.Interleukin-6 (IL-6) induces vascular endothelial growth factor (VEGF) expression. This study demonstrates that treatment of various cell lines with IL-6 for 6–48 hours significantly induces VEGF mRNA, comparable to hypoxia or cobalt chloride. The effect of IL-6 is mediated by 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 it plays a role in VEGF expression through transcriptional and post-transcriptional control mechanisms. VEGF is a potent angiogenic agent that acts as a mitogen for vascular endothelial cells. It is encoded by a single gene and produces four isoforms through alternative splicing. The 165-amino acid isoform is the most abundant. VEGF expression is regulated by various factors, including hypoxia, cytokines, and growth factors. The study shows that IL-6 induces VEGF expression, which may promote angiogenesis indirectly. The 5'-UTR of VEGF is essential for its expression and contains DNA motifs that work cooperatively with promoter elements. The results suggest that IL-6 should be considered an indirect inducer of angiogenesis through VEGF expression. The study also shows that other cytokines, such as IFN-β and TNF-α, can induce VEGF expression. The 5'-UTR of VEGF is important for its expression and may be involved in translational regulation. The study provides evidence that IL-6 induces VEGF expression through specific DNA motifs in the promoter and 5'-UTR regions. The results indicate that the secondary structure of the 5'-UTR may be important for efficient VEGF expression and suggest that transcription and post-transcriptional control mechanisms are involved.