IL-20 is expressed in atherosclerosis plaques and promotes atherosclerosis in apolipoprotein E-deficient mice.
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.


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.
Chen
Wei-Yu
WY
Institute of Basic Medical Sciences, National Cheng Kung University, College of Medicine, Tainan 704, Taiwan.
Cheng
Bor-Chih
BC
Jiang
Meei-Jyh
MJ
Hsieh
Mei-Yi
MY
Chang
Ming-Shi
MS
D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency*; D050197:Atherosclerosis / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D006528:Carcinoma, Hepatocellular / Q000098:blood supply; D018925:Chemokines / Q000378:metabolism; D005263:Femoral Artery / Q000378:metabolism; D006801:Humans; D000860:Hypoxia / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000493:pharmacokinetics / Q000494:pharmacology; D008114:Liver Neoplasms, Experimental / Q000098:blood supply; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000209:etiology; D018123:Receptors, Interleukin / Q000378:metabolism; D015854:Up-Regulation
D001057:Apolipoproteins E; D018925:Chemokines; D008077:Lipoproteins, LDL; D018123:Receptors, Interleukin; C099252:oxidized low density lipoprotein; D016753:Interleukin-10