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Involvement of L-type Ca2+ channel and toll-like receptor-4 in nickel-induced interleukin-8 gene expression

Authors

  • Chia-Hsien Lin,

    1. Department of Health Industry Management, School of Health Care Management, Kainan University, Taoyuan, Taiwan
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    • These authors contributed equally to this work.

  • Chih-Ang Chung,

    1. Department of Biochemistry, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
    2. Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei, Taiwan
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    • These authors contributed equally to this work.

  • Jhen-Hong Wong,

    1. Department of Biochemistry, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
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  • Ben-Kuen Chen,

    1. Institute of Bioinformatics and Biosignal Transduction, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, Taiwan
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  • Siou-Jin Chiu,

    1. Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei, Taiwan
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  • Sukhontip Klahan,

    1. Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei, Taiwan
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  • Yi-Chao Lee,

    1. Ph.D. Program for Neural Regenerative Medicine, College of Medical Science and Technology, Center for Neurotrauma and Neuroregeneration, Taipei Medical University, Taipei, Taiwan
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  • Wei-Chiao Chang

    Corresponding author
    1. Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei, Taiwan
    2. Department of Pharmacy, Taipei Medical University-Wan Fang Hospital, Taipei, Taiwan
    3. Master Program for Clinical Pharmacogenomics and Pharmacoproteomics, School of Pharmacy, Taipei Medical University, Taipei, Taiwan
    4. Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
    5. Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
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ABSTRACT

The metal nickel (Ni2+) is found everywhere in our daily lives, including coins, costume jewelry, and even nuts and chocolates. Nickel poisoning can cause inflammatory reactions, respiratory diseases, and allergic contact dermatitis. To clarify the mechanism by which nickel induces mediators of inflammation, we used the human acute monocytic leukemia THP-1 cell line as a model. Interleukin (IL)-8 promoter activity as well as gene expression were tested by luciferase assay and real-time polymerase chain reaction. The underlying mechanisms of nickel-induced IL-8 were investigated. We found that nickel induced IL-8 gene expression via the L-type Ca2+ channel, Toll-like receptor-4 (TRL-4) and nuclear factor NF-κB signal transduction pathways. Nickel activated NF-κB expression through extracellular signal-regulated kinase 1/2 phosphorylation and then increased IL-8 expression. Thus, the L-type Ca2+ channel and TRL-4 play important roles in nickel-induced inflammatory gene expressions. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 5–12, 2016.

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