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Cytokine. 2010 Jan;49(1):73-9. doi: 10.1016/j.cyto.2009.08.009. Epub 2009 Oct 12.

Oxidative mechanisms of IL-4-induced IL-6 expression in vascular endothelium.

Author information

1
Laboratory of Vascular Biology, Department of Biomedical Sciences and Pathobiology, School of Biomedical Engineering and Sciences, Virginia Tech, Blacksburg, VA 24061, USA. ywlee@vt.edu

Abstract

The present study is designed to investigate the effects of interleukin-4 (IL-4) on expression of interleukin-6 (IL-6), as well as to examine the role of distinct sources of reactive oxygen species (ROS) in this process. Real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) showed that IL-4 significantly up-regulated the mRNA and protein expression of IL-6 in human aortic endothelial cells (HAEC) and C57BL/6 mice. Dihydroethidium (DHE) and dichlorofluorescein (DCF) fluorescence staining demonstrated that IL-4 significantly increased ROS generation in HAEC. A significant and dose-dependent inhibition of IL-4-induced IL-6 expression was observed in HAEC pre-treated with antioxidants, such as pyrrolidine dithiocarbamate (PDTC) and epigallocatechin gallate (EGCG), indicating that IL-4-induced IL-6 expression is mediated via an ROS-dependent mechanism. Additionally, pharmacological inhibitor of NADPH oxidase (NOX) significantly attenuated IL-4-induced ROS generation and IL-6 expression in HAEC. Furthermore, the disruption of NOX gene dramatically and significantly reduced IL-4-induced IL-6 expression in NOX knockout mice (B6.129S6-Cybb(tm1Din)/J). In contrast, overexpression of IL-6 in IL-4-activated HAEC was not affected by inhibiting other ROS generating pathways, such as xanthine oxidase, arachidonic acid metabolism, and the mitochondrial electron transport chain. These results demonstrate that IL-4 up-regulates IL-6 expression in vascular endothelium through NOX-mediated ROS generation.

PMID:
19822443
PMCID:
PMC2808430
DOI:
10.1016/j.cyto.2009.08.009
[Indexed for MEDLINE]
Free PMC Article

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