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Submitted on December 16, 2005
Accepted on June 5, 2006
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.
* To whom correspondence should be addressed. 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. IL-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 HUVECs in response to hypoxic treatment. Incubating IL-20 with HUVECs 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.
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