Abstract
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-1beta (IL-1beta), could induce lymphangiogenesis in mouse cornea through enhanced production of potent lymphangiogenic factors, VEGF-A, VEGF-C and VEGF-D. IL-1beta-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-1beta implanted cornea. Depletion of macrophages by a bisphosphonate encapsulated in liposomes inhibited this IL-1beta-induced lymphangiogenesis and also up-regulation of VEGF-A, VEGF-C, and VEGF-D. Furthermore, IL-1beta-induced lymphangiogenesis and angiogenesis were suppressed by NF-kappaB inhibition with marked suppression of VEGF-A, VEGF-C, and VEGF-D expression.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Cell Proliferation
-
Cornea / blood supply
-
Cornea / drug effects
-
Cornea / immunology
-
Diphosphonates / pharmacology
-
Fibroblast Growth Factor 2 / biosynthesis
-
Fibroblast Growth Factor 2 / genetics
-
Fibroblast Growth Factor 2 / pharmacology
-
Humans
-
Interleukin-1beta / immunology*
-
Interleukin-1beta / pharmacology
-
Keratitis / immunology*
-
Lymphangiogenesis / drug effects
-
Lymphangiogenesis / genetics
-
Lymphangiogenesis / immunology*
-
Macrophages / immunology*
-
Mice
-
Mice, Inbred C57BL
-
NF-kappa B / agonists
-
NF-kappa B / antagonists & inhibitors
-
NF-kappa B / metabolism*
-
Neovascularization, Pathologic / immunology
-
Vascular Endothelial Growth Factor C / biosynthesis*
-
Vascular Endothelial Growth Factor C / genetics
-
Vascular Endothelial Growth Factor C / pharmacology
-
Vascular Endothelial Growth Factor D / biosynthesis*
-
Vascular Endothelial Growth Factor D / genetics
-
Vascular Endothelial Growth Factor D / pharmacology
Substances
-
Diphosphonates
-
Interleukin-1beta
-
NF-kappa B
-
Vascular Endothelial Growth Factor C
-
Vascular Endothelial Growth Factor D
-
Fibroblast Growth Factor 2