The anti-angiogenic activity of IL-12 is increased in iNOS−/− mice and involves NK cells

We have previously reported that the in vivo transfer of murine interleukin-12 (IL-12) gene using a Semliki Forest virus vector induced tumor regression through inhibition of tumor blood vessel formation. To examine whether IL-12 anti-angiogenic activity interferes with the NO pathway, we used induc...

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Veröffentlicht in:Journal of molecular medicine (Berlin, Germany) Germany), 2010-08, Vol.88 (8), p.775-784
Hauptverfasser: Bielawska-Pohl, Aleksandra, Blesson, Séverine, Benlalam, Houssem, Trenado, Aurélie, Opolon, Paule, Bawa, Olivia, Rouffiac, Valérie, Dus, Danuta, Kieda, Claudine, Chouaib, Salem
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container_issue 8
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container_title Journal of molecular medicine (Berlin, Germany)
container_volume 88
creator Bielawska-Pohl, Aleksandra
Blesson, Séverine
Benlalam, Houssem
Trenado, Aurélie
Opolon, Paule
Bawa, Olivia
Rouffiac, Valérie
Dus, Danuta
Kieda, Claudine
Chouaib, Salem
description We have previously reported that the in vivo transfer of murine interleukin-12 (IL-12) gene using a Semliki Forest virus vector induced tumor regression through inhibition of tumor blood vessel formation. To examine whether IL-12 anti-angiogenic activity interferes with the NO pathway, we used inducible nitric oxide synthase-deficient mice (iNOS − / − ) and demonstrated that the anti-tumor effect of IL-12 is more pronounced in these mice. In addition, despite the increased level of intratumoral VEGF in iNOS − / − mice, IL-12 induced a stronger inhibition of blood vessel formation. Histological analysis of SFV-IL-12-treated tumors showed an increase in natural killer (NK) perivascular infiltration in iNOS − / − as compared to control mice. In vitro IL-12-stimulated murine splenic NK cells displayed significant killing activity towards established murine endothelial cells used as targets. These studies indicate that the anti-angiogenic activity of IL-12 interferes with iNOS pathway and involves NK cell recruitment.
doi_str_mv 10.1007/s00109-010-0620-7
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subjects Animals
Biological and medical sciences
Biomedical and Life Sciences
Biomedicine
Endothelial Cells - pathology
Gene Knockout Techniques
General aspects
Human Genetics
Interleukin-12 - immunology
Internal Medicine
Killer Cells, Natural - immunology
Killer Cells, Natural - pathology
Medical sciences
Melanoma, Experimental - blood supply
Melanoma, Experimental - immunology
Melanoma, Experimental - pathology
Mice
Mice, Inbred C57BL
Molecular Medicine
Neovascularization, Pathologic - immunology
Neovascularization, Pathologic - pathology
Nitric Oxide - immunology
Nitric Oxide Synthase Type II - genetics
Original Article
Semliki Forest virus
Vascular Endothelial Growth Factor A - immunology
title The anti-angiogenic activity of IL-12 is increased in iNOS−/− mice and involves NK cells
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