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

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-1 beta (IL-1 beta), could induce lymphangiogenesis in Mouse Cornea through enhanced production of potent lymphangiogenic factors. VEGF-A, VEGF-C and VEGF-D. IL-1 beta-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-1 beta implanted cornea. Depletion of macrophages by a bisphosphonate encapsulated in liposomes inhibited this IL-1 beta-induced lymphangiogenesis and also up-regulation of VEGF-A. VEGF-C, and VEGF-D. Furthermore, IL-1 beta-induced lymphangiogenesis and angiogenesis were suppressed by NF-kappa B inhibition with marked suppression of VEGF-A. VEGF-C, and VEGF-D expression. (C) 2008 Elsevier Inc. All rights reserved.