IL-20 Is Expressed in Atherosclerosis Plaques and Promotes Atherosclerosis in Apolipoprotein E–Deficient Mice

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Abstract
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.