title: Involvement of L-type Ca²⁺ channel and toll-like receptor-4 in nickel-induced interleukin-8 gene expression.
abstract: The metal nickel (Ni(2+)) 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 Ca(2+) 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 Ca(2+) channel and TRL-4 play important roles in nickel-induced inflammatory gene expressions.
authors.affiliation: Department of Health Industry Management, School of Health Care Management, Kainan University, Taoyuan, Taiwan.
authors.forename: Chia-Hsien
authors.initials: CH
authors.lastname: Lin
authors.affiliation: Department of Biochemistry, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei, Taiwan.
authors.forename: Chih-Ang
authors.initials: CA
authors.lastname: Chung
authors.affiliation: Department of Biochemistry, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Jhen-Hong
authors.initials: JH
authors.lastname: Wong
authors.affiliation: Institute of Bioinformatics and Biosignal Transduction, College of Bioscience and Biotechnology, National Cheng Kung University, Tainan, 701, Taiwan.
authors.forename: Ben-Kuen
authors.initials: BK
authors.lastname: Chen
authors.affiliation: Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei, Taiwan.
authors.forename: Siou-Jin
authors.initials: SJ
authors.lastname: Chiu
authors.affiliation: Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei, Taiwan.
authors.forename: Sukhontip
authors.initials: S
authors.lastname: Klahan
authors.affiliation: Ph.D. Program for Neural Regenerative Medicine, College of Medical Science and Technology, Center for Neurotrauma and Neuroregeneration, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yi-Chao
authors.initials: YC
authors.lastname: Lee
authors.affiliation: Department of Clinical Pharmacy, School of Pharmacy, Taipei Medical University, Taipei, Taiwan.|Department of Pharmacy, Taipei Medical University-Wan Fang Hospital, Taipei, Taiwan.|Master Program for Clinical Pharmacogenomics and Pharmacoproteomics, School of Pharmacy, Taipei Medical University, Taipei, Taiwan.|Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.|Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Wei-Chiao
authors.initials: WC
authors.lastname: Chang
mesh_terms: D020746:Calcium Channels, L-Type / Q000378:metabolism*; D045744:Cell Line, Tumor; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D009532:Nickel / Q000737:chemistry / Q000633:toxicity*; D010766:Phosphorylation / Q000187:drug effects; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
chemical_list: C508606:CXCL8 protein, human; D020746:Calcium Channels, L-Type; D016209:Interleukin-8; D016328:NF-kappa B; D034741:RNA, Small Interfering; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D009532:Nickel; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
keywords: L-type Ca2+ channel; TLR4; human acute monocytic leukemia; nickel