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AP-1 and NF-κB transcriptionally regulate interleukin-8 in EA.Hy926 cells under shear stress

Authors

  • Yi Zhang,

    Corresponding author
    1. Laboratory of Biomedical Ultrasonics and Gynecologic cancers, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, Peoples Republic of China
    2. Department of Obstetric and Gynecologic, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, Peoples Republic of China
    3. Key Laboratory of Obstetric and Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, Chengdu, Sichuan, Peoples Republic of China
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  • Yi Lai,

    Corresponding author
    1. Chengdu Womans and Childrens Medical Center Hospital, Chong Qing Medical University, Chengdu, Sichuan, Peoples Republic of China
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  • Huai-Qing Chen,

    Corresponding author
    1. Institute of Biomedical Engineering, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, Sichuan, Peoples Republic of China
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  • Ying-Feng Liu

    1. Laboratory of Biomedical Ultrasonics and Gynecologic cancers, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, Peoples Republic of China
    2. Department of Obstetric and Gynecologic, West China Second University Hospital, Sichuan University, Chengdu, Sichuan, Peoples Republic of China
    3. Key Laboratory of Obstetric and Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, Chengdu, Sichuan, Peoples Republic of China
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These authors contributed equally to this work.

To whom correspondence should be addressed (email chq@scu.edu.cn).

Abstract

Cardiovascular and cerebrovascular diseases remain the leading cause of death in the world. AS (atherosclerosis) is not only an inflammatory disease in which chemokines play the main role but also a disorder that is related to blood SS (shear stress). We have investigated the action of IL-8 (interleukin-8) mRNA expression in human endothelial cells line-EA.Hy926 under SS at different intensities and duration. Expression increases with time in an intensity dependent manner. With regard to the transcriptional mechanism involved, transient transfection of the human wild-type IL-8 promoter (–162/+44)/luciferase reporter plasmid, or site mutation of one of the binding sites [AP-1 (activator protein 1) or NF-κB (nuclear factor κB)] in the IL-8 promoter region was investigated. Both AP-1 and NF-κB were essential for SS-activated transcription, with the cells responding to NF-κB activation within minutes. After stimulated at low SS (4.20 dyne/cm2) for 30 min, the P65 subunit was translocated from the cytoplasm to nucleus for at least 60 min, while the cytoplasmic level of IκB (inhibitory κB) gradually decreased. The combined activation of NF-κB and AP-1 are the upstream regulators of low SS-induced IL-8 production in EA.Hy926 cells, which subsequently trigger an inflammatory reaction in endothelium.

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