Published online before print June 15, 2006, doi: 10.1161/01.ATV.0000232502.88144.6f
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© 2006 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
IL-20 Is Expressed in Atherosclerosis Plaques and Promotes Atherosclerosis in Apolipoprotein E–Deficient Mice
From the Institute of Basic Medical Sciences (W.Y.C., B.C.C., M.S.C.), Department of Biochemistry and Molecular Biology (W.Y.C., M.Y.H., M.S.C.), Department of Cell Biology and Anatomy (M.J.J.), College of Medicine, National Cheng Kung University, and Chi-Mei Medical Center (W.Y.C., B.C.C., M.S.C.), Tainan, Taiwan.
Correspondence to Ming-shi Chang, Department of Biochemistry and Molecular Biology, National Cheng Kung University, College of Medicine, Tainan 704, Taiwan. E-mail mschang{at}mail.ncku.edu.tw
Objective— Atherosclerosis is a chronic inflammatory disease with immune cell infiltration. Various cytokines and chemokines have been characterized as pro- or antiatherogenic factors. Interleukin-20 (IL-20) belongs to the IL-10 family and is a proinflammatory cytokine involved in the pathogenesis of psoriasis. However, the association between IL-20 and atherosclerosis is undetermined. Therefore, we sought to investigate whether IL-20 is associated with atherosclerosis.
Methods and Results— We examined the expression of IL-20 and its receptor complex IL-20R1/IL-20R2 in atherosclerotic lesions of humans and mice using immunohistochemical staining. IL-20 was expressed in macrophage-rich areas. Both IL-20 and IL-20R1/IL-20R2 were expressed by endothelial cells lining the intimal microvessels, vasa vasorum, but rarely in nonatherosclerotic arteries. We used reverse-transcription polymerase chain reaction to analyze gene expression. IL-20 transcripts increased in hypoxic monocytes and monocytes treated with oxidized low-density lipoprotein. The expression of IL-20R1 and IL-20R2 was also upregulated by human umbilical vein endothelial cells in response to hypoxic treatment. Incubating IL-20 with human umbilical vein endothelial cells upregulated CXCL9 and CXCL11 transcripts. Furthermore, in vivo administration of IL-20 expression vector using intramuscular electroporation promoted atherosclerosis in apolipoprotein E-deficient mice.
Conclusions— Our data suggest that IL-20 is a proatherogenic cytokine that contributes to the progression of atherosclerosis.
We investigated the association between IL-20 and atherosclerosis. IL-20 and its receptors are expressed in the atherosclerosis plaques of human and mice. In vitro, oxidized LDL and hypoxia induced IL-20. In vivo, IL-20 promoted atherosclerosis in apoE–/– mice. Thus, we postulate that IL-20 is a proatherogenic cytokine.
Key Words: atherosclerosis • cytokines • hypoxia • IL-20 • oxidized lipids
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Arterioscler Thromb Vasc Biol 2006 26: 1929-1930.
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