Role of macrophages in inflammatory lymphangiogenesis: Enhanced production of vascular endothelial growth factor C and D through NF-kappaB activation |
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Authors: | Watari Kosuke Nakao Shintaro Fotovati Abbas Basaki Yuji Hosoi Fumihito Bereczky Biborka Higuchi Ryuichi Miyamoto Tomofumi Kuwano Michihiko Ono Mayumi |
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Affiliation: | a Department of Pharmaceutical Oncology, Graduate School of Pharmaceutical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan b Department of Natural Products Chemistry, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan c Innovation Center for Medical Redox Navigation, Kyushu University, Fukuoka 812-8582, Japan |
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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-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. |
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Keywords: | IL-1β Lymphangiogenesis Inflammation VEGF-C VEGF- D VEGFR-3 Macrophage |
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