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Article Dans Une Revue Journal of Molecular Medicine Année : 2010

The antiangiogenic activtivity of IL-12 is increased in iNOS-/- mice and involves NK cells

Séverine Blesson
  • Fonction : Auteur
Benlalam Houssem
Aurélie Trenado
  • Fonction : Auteur
Paule Opolon
  • Fonction : Auteur
Olivia Bawa
  • Fonction : Auteur
Valérie Rouffiac
  • Fonction : Auteur
Dus Danuta
  • Fonction : Auteur

Résumé

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.

Dates et versions

hal-00529248 , version 1 (25-10-2010)

Identifiants

Citer

Aleksandra Bielawska-Pohl, Séverine Blesson, Benlalam Houssem, Aurélie Trenado, Paule Opolon, et al.. The antiangiogenic activtivity of IL-12 is increased in iNOS-/- mice and involves NK cells. Journal of Molecular Medicine, 2010, 88 (8), pp.775-784. ⟨10.1007/s00109-010-0620-7⟩. ⟨hal-00529248⟩
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