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

被引：106

作者：

Kempe, Sybille ^{[1
]}

Heinz, Philipp ^{[2
]}

Kokai, Enikoe ^{[1
]}

Devergne, Odile ^{[3
]}

Marx, Nikolaus ^{[2
]}

Wirth, Thomas ^{[1
]}

机构：

[1] Univ Ulm, Inst Physiol Chem, D-89081 Ulm, Germany

[2] Univ Ulm, Dept Internal Med 2, D-89081 Ulm, Germany

[3] Hop Necker Enfants Malad, CNRS, UMR 8147, Paris, France

来源：

AMERICAN JOURNAL OF PATHOLOGY | 2009年 / 175卷 / 01期

关键词：

NF-KAPPA-B; PROLIFERATOR-ACTIVATED RECEPTORS; SMOOTH-MUSCLE CELLS; CD4(+) T-CELLS; ATHEROSCLEROTIC PLAQUES; INFLAMMATORY RESPONSE; TH1; RESPONSES; CUTTING EDGE; CYTOKINE; IL-27;

D O I：

10.2353/ajpath.2009.080752

中图分类号：

R36 [病理学];

学科分类号：

100103 [病原生物学];

摘要：

Atherosclerosis is characterized by a complex immune response in the vessel wall, involving both inflammation and autoinumme 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-a 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. (Am J Pathol 2009,175:440-447; DOI: 10.2353/ajpath.2009.080752)

引用

页码：440 / 447

页数：8

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[1]

Cutting edge:: Early IL-4 production governs the requirement for IL-27-WSX-1 signaling in the development of protective Th1 cytokine responses following Leishmania major infection [J].