Gene expression profile in interleukin-4-stimulated human vascular endothelial cells.
Interleukin-4 (IL-4)-mediated pro-oxidative and pro-inflammatory vascular environments have been implicated in the pathogenesis of atherosclerosis. The cellular and molecular regulatory mechanisms underlying this process, however, are not fully understood. In the present study, we employed GeneChip microarray analysis to investigate global gene expression patterns in human vascular endothelial cells after treatment with IL-4. Our results showed that mRNA levels of a total of 106 genes were significantly up-regulated and 41 genes significantly down-regulated with more than a 2-fold change. The majority of these genes are critically involved in the regulation of inflammatory responses, apoptosis, signal transduction, transcription factors, and metabolism; functions of the remaining genes are unknown. The changes in gene expression of selected genes related to inflammatory reactions, such as vascular cell adhesion molecule-1 (VCAM-1), E-selectin, monocyte chemoattractant protein-1 (MCP-1), and interleukin-6 (IL-6), were verified by quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) analyses. IL-4 treatment also significantly increased the adherence of inflammatory cells to endothelial cell monolayers in a dose-dependent manner. These results may help determine the molecular mechanisms of action of IL-4 in human vascular endothelium. In addition, a better understanding of IL-4-induced vascular injury at the level of gene expression could lead to the identification of new therapeutic strategies for atherosclerosis.
Lee
Yong Woo
YW
Department of Surgery/Division of Neurosurgery, University of Kentucky College of Medicine, 800 Rose Street, Lexington, Kentucky 40536, USA. ylee2@uky.edu
Eum
Sung Yong
SY
Chen
Kuey Chu
KC
Hennig
Bernhard
B
Toborek
Michal
M
D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D015847:Interleukin-4 / Q000494:pharmacology*; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics
D018836:Inflammation Mediators; D012333:RNA, Messenger; D014157:Transcription Factors; D015847:Interleukin-4