Role of macrophages in inflammatory lymphangiogenesis: Enhanced production of vascular endothelial growth factor C and D through NF-κB activation

• Published in: Biochemical and biophysical research communications 2008-12, Vol.377 (3), p.826-831
• Main Authors: Watari, Kosuke, Nakao, Shintaro, Fotovati, Abbas, Basaki, Yuji, Hosoi, Fumihito, Bereczky, Biborka, Higuchi, Ryuichi, Miyamoto, Tomofumi, Kuwano, Michihiko, Ono, Mayumi
• Format: Article
• Language: English
• Subjects: IL-1β; Inflammation; Lymphangiogenesis; Macrophage; VEGF- D; VEGF-C; VEGFR-3
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2008.10.077

The close association of inflammation, angiogenesis and cancer progression is now highlighted, and in this study we especially focused on a close association of inflammation and lymphangiogenesis. We found that proinflammatory cytokine, interleukin-1β (IL-1β), could induce lymphangiogenesis in mouse cornea through enhanced production of potent lymphangiogenic factors, VEGF-A, VEGF-C and VEGF-D. IL-1β-induced lymphangiogenesis, but not angiogenesis, was inhibited by administration of a selective anti-VEGF receptor-3 (VEGFR-3) neutralizing antibody. And in mouse cornea we observed recruitment of monocyte/macrophages and neutrophils by IL-1β implanted cornea. Depletion of macrophages by a bisphosphonate encapsulated in liposomes inhibited this IL-1β-induced lymphangiogenesis and also up-regulation of VEGF-A, VEGF-C, and VEGF-D. Furthermore, IL-1β-induced lymphangiogenesis and angiogenesis were suppressed by NF-κB inhibition with marked suppression of VEGF-A, VEGF-C, and VEGF-D expression.