Involvement of nitric oxide in the inhibition of angiogenesis by interleukin-2.
Interleukin-2 (IL-2), an immunoregulatory cytokine possessing antitumour activity, is an inducer of nitric oxide (NO) synthesis in mice and man. In this study, the possibility that IL-2 possesses antiangiogenic properties that account for its antitumour effects in vivo was examined. IL-2 caused a dose-dependent inhibition of angiogenesis in the chick embryo chorioallantoic membrane (CAM). This inhibition was completely reversed by the NO synthase inhibitor N(G)-nitro-L-arginine methylester (L-NAME). Furthermore, IL-2 was capable of stimulating NO synthase activity in the CAM in vitro and this effect was suppressed by L-NAME. Addition of IL-2 to human umbilical vein endothelial cells (HUVECs) in culture, had no effect on their growth characteristics. These results suggest that IL-2 may be an important antiangiogenic molecule causing its effect via nitric oxide synthesis. The antiangiogenic activity of IL-2 may be, at least in part, responsible for its antitumour properties.
Sakkoula
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Department of Pharmacology, Medical School, University of Patras, Greece.
Pipili-Synetos
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Maragoudakis
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ME
D000482:Allantois / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D002642:Chick Embryo; D002823:Chorion / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009389:Neovascularization, Pathologic; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D014471:Umbilical Veins / Q000187:drug effects
D004791:Enzyme Inhibitors; D007376:Interleukin-2; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester