Inflammation Research

, Volume 59, Issue 9, pp 755–765 | Cite as

Role of NADPH oxidase in interleukin-4-induced monocyte chemoattractant protein-1 expression in vascular endothelium

  • Yong Woo Lee
  • Won Hee Lee
  • Paul H. Kim
Original Research Paper


Objective and design

The pro-oxidative and pro-inflammatory pathways in vascular endothelium have been implicated in the development of atherosclerosis. In the present study, we investigated effect of interleukin-4 (IL-4) on monocyte chemoattractant protein-1 (MCP-1) expression in vascular endothelium and examined the role of distinct sources of reactive oxygen species (ROS) in this process.

Methods and results

Real-time reverse transcriptase-polymerase chain reaction and enzyme-linked immunosorbent assay showed that IL-4 significantly up-regulated mRNA and protein expression of MCP-1 in human aortic endothelial cells (HAEC) and C57BL/6 mice. A significant and dose-dependent inhibition of IL-4-induced MCP-1 expression was observed in HAEC pre-treated with antioxidants, such as pyrrolidine dithiocarbamate and epigallocatechin gallate, indicating that IL-4-induced MCP-1 expression is mediated via a ROS-dependent mechanism. Additionally, pharmacological inhibitors of NADPH oxidase (NOX) significantly attenuated IL-4-induced MCP-1 expression in HAEC. Furthermore, the disruption of the NOX gene dramatically reduced IL-4-induced MCP-1 expression in NOX knockout mice (B6.129S6-Cybbtm1Din/J). In contrast, overexpression of MCP-1 in IL-4-stimulated HAEC was not affected by inhibiting other ROS generating pathways, such as xanthine oxidase and the mitochondrial electron transport chain.


These results demonstrate that IL-4 up-regulates MCP-1 expression in vascular endothelium through NOX-mediated ROS generation.


NADPH oxidase IL-4 MCP-1 Reactive oxygen species Vascular endothelium 



This study was supported in part by Grants from National Institutes of Health/National Heart, Lung, and Blood Institute (HL085229) and National Science Foundation Macromolecular Interfaces with Life Sciences-Integrative Graduate Education and Research Traineeship (MILES-IGERT).


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Copyright information

© Springer Basel AG 2010

Authors and Affiliations

  1. 1.Laboratory of Vascular Biology, Department of Biomedical Sciences and Pathobiology, School of Biomedical Engineering and SciencesVirginia Polytechnic Institute and State University (Virginia Tech)BlacksburgUSA
  2. 2.School of Biomedical Engineering and SciencesVirginia Polytechnic Institute and State University (Virginia Tech)BlacksburgUSA

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