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(American Journal of Pathology. 2009;175:440-447.)
© 2009 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2009.080752

Epstein-Barr Virus-Induced Gene-3 Is Expressed in Human Atheroma Plaques

Sybille Kempe*, Philipp Heinz{dagger}, Enikö Kokai*, Odile Devergne{ddagger}, Nikolaus Marx{dagger} and Thomas Wirth*

From the Institute of Physiological Chemistry,* and the Department of Internal Medicine II,{dagger} University of Ulm, Ulm, Germany; and Centre National de la Recherche Scientifique,{ddagger} Unité Mixte de Recherche 8147, Hôpital Necker, Bâtiment Sèvres, Paris, France

Atherosclerosis is characterized by a complex immune response in the vessel wall, involving both inflammation and autoimmune processes. Epstein-Barr virus-induced gene 3 (Ebi3) is a member of the interleukin (IL)-12 heterodimeric cytokine family, which has important immunomodulatory functions. To date, little is known about the role of Ebi3 in vascular disease. We examined the expression of Ebi3 in human atheromatous lesions and analyzed its transcriptional regulation in vascular cells. The in situ expression of Ebi3 in human endarterectomy specimens was analyzed by immunohistochemistry. In these lesions, smooth muscle cells expressed Ebi3 as well as the IL-27{alpha}/p28 and IL-12{alpha}/p35 subunits. Primary aortic smooth muscle cells up-regulated Ebi3 in response to proinflammatory stimuli like tumor necrosis factor-{alpha} and interferon-{gamma}. Interestingly, pretreatment of these cells with the peroxisome proliferator-activated receptor-{gamma} agonist rosiglitazone strongly reduced Ebi3 induction. Chromatin immunoprecipitation experiments revealed that this inhibition is due to interference with p65/RelA recruitment to the Ebi3 promoter. Our data support a possible role of Ebi3 in atherogenesis either as homodimer or as IL-27/IL-35 heterodimer, and suggest that Ebi3 could be an interesting target for therapeutic manipulation in atherosclerosis.






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Copyright © 2009 by the American Society for Investigative Pathology.