Open Access

ARTICLE

In vivo electrotransfer of interleukin-10 cDNA prevents endothelial upregulation of activated NF-κB and adhesion molecules following an atherogenic diet

Stéphane Potteaux¹, Virginie Deleuze², Régine Merval¹, Michel F. Bureau^2,3, Bruno Esposito¹, Daniel Scherman^2,3, Alain Tedgui¹, Ziad Mallat¹

1 Centre de Recherche Cardiovasculaire Inserm Lariboisière, U689, Paris
2 Unité Mixte de Recherche, Centre National de la Recherche Scientifique, 133, Vitry-sur-Seine; and Aventis, Vitry-sur-seine
3 Present address: Unité de Pharmacologie chimique et Génétique, Inserm U 640 CNRS UMR 8151, Faculté de Pharmacie, 4 av de l’observatoire, 75270 Paris Cedex 06

* Corresponding Author: Z. Mallat,

European Cytokine Network 2006, 17(1), 13-18.

Accepted 13 February 2006;

Abstract

Objectives. Interleukin (IL)-10 has anti-atherogenic properties. However, the molecular mechanisms involved in IL-10 protection against atherosclerosis in vivo remain poorly understood. In this study, we examined the effect of IL-10 cDNA in vivo electrotransfer on diet-induced, endothelial activation. Methods. C57BL/6J mice were fed an atherogenic diet for 10 days. Expression of VCAM-1 and ICAM-1 was examined in the aortic sinus, a region predisposed to atherogenesis in mice, using immunohistochemistry. NF-κB activation was examined using a monoclonal antibody that selectively reacts with the activated form of the p65 subunit. Results. We detected a low basal expression of activated NF-κB, VCAM-1 and ICAM-1 in the endothelium of the aortic sinus. Endothelial expression of activated NF-κB, VCAM-1 and ICAM-1 was markedly increased after 10 days on the atherogenic diet (p < 0.001). In vivo electrotransfer of a murine IL-10-encoding plasmid completely prevented diet-induced endothelial upregulation of activated NF-κB, VCAM-1 and ICAM-1 (p < 0.01). Conclusion. In vivo electrotransfer of IL-10 cDNA prevents diet-induced endothelial activation. These results suggest that the protective effects of IL-10 may already occur in the very early stages of atherogenesis.

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