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

作者: Yong Woo Lee , Won Hee Lee , Paul H. Kim

DOI: 10.1016/J.CYTO.2009.08.009

关键词: NADPH oxidaseMolecular biologyXanthine oxidaseEpigallocatechin gallateKnockout mouseOxidative phosphorylationBiologyReactive oxygen speciesDichlorofluoresceinPyrrolidine dithiocarbamateImmunologyImmunology and AllergyBiochemistryHematology

摘要: The present study is designed to investigate the effects of interleukin-4 (IL-4) on expression interleukin-6 (IL-6), as well examine role distinct sources 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 mRNA protein IL-6 human aortic endothelial cells (HAEC) C57BL/6 mice. Dihydroethidium (DHE) dichlorofluorescein (DCF) fluorescence staining demonstrated increased ROS generation HAEC. A significant dose-dependent inhibition IL-4-induced was observed HAEC pre-treated with antioxidants, such pyrrolidine dithiocarbamate (PDTC) epigallocatechin gallate (EGCG), indicating mediated via an ROS-dependent mechanism. Additionally, pharmacological inhibitor NADPH oxidase (NOX) attenuated Furthermore, disruption NOX gene dramatically reduced knockout mice (B6.129S6-Cybbtm1Din/J). In contrast, overexpression IL-4-activated not affected by inhibiting other generating pathways, xanthine oxidase, arachidonic acid metabolism, mitochondrial electron transport chain. These results demonstrate up-regulates vascular endothelium through NOX-mediated generation.

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