title: Toxicity of nickel ions and comprehensive analysis of nickel ion-associated gene expression profiles in THP-1 cells.
abstract: The aim of the present study was to explore the toxic effects and underlying mechanisms of nickel ions during therapeutic nickel‑based alloy‑treatment in congenital heart disease by investigating the metal‑induced cytotoxicity to the human monocyte‑derived macrophage cell line THP‑1. THP‑1 cells were treated with NiCl2·6H2O (25, 50, 100, 200, 400 and 800 µM) for 24, 48 and 72 h, respectively. MTT was applied to detect THP‑1 cell proliferation following NiCl2 treatment. Apoptosis of THP‑1 cells was quantified using flow cytometry. Illumina sequencing was used for screening the associated genes, whose mRNA expression levels were further confirmed by quantitative real‑time polymerase chain reaction. High concentrations of nickel ions had a significant suppressive effect on cell proliferation at the three concentrations investigated (200, 400 and 800 µM). Treatment with nickel ions (25‑400 µM) for 48 h reduced cell viability in a dose‑dependent manner. The mRNA expression levels of RELB, FIGF, SPI‑1, CXCL16 and CRLF2 were significantly increased following nickel treatment. The results of the present study suggested that nickel ions exert toxic effects on THP‑1 cell growth, which may indicate toxicity of the nickel ion during treatment of congenital heart disease. The identification of genes modified by the toxic effects of nickel on THP‑1 cells (EPOR, RELB, FIGF, SPI‑1, TGF‑β1, CXCL16 and CRLF2) may aid in the development of interventional measures for the treatment/prevention of nickel ion‑associated toxic effects during the treatment of congenital heart disease.
authors.affiliation: Department of Cardiology, Guangdong Provincial Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510180, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pediatric Cardiology, Guangdong Provincial Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510180, P.R. China.
authors.forename: Zhi-Wei
authors.initials: ZW
authors.lastname: Zhang
authors.affiliation: Department of Pediatric Cardiology, Guangdong Provincial Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510180, P.R. China.
authors.forename: Yu-Mei
authors.initials: YM
authors.lastname: Xie
authors.affiliation: Department of Pediatric Cardiology, Guangdong Provincial Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510180, P.R. China.
authors.forename: Shu-Shui
authors.initials: SS
authors.lastname: Wang
authors.affiliation: Department of Pediatric Cardiology, Guangdong Provincial Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510180, P.R. China.
authors.forename: Qing-Huan
authors.initials: QH
authors.lastname: Qiu
authors.affiliation: Department of Cardiology, Guangdong Provincial Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510180, P.R. China.
authors.forename: Ying-Ling
authors.initials: YL
authors.lastname: Zhou
authors.affiliation: Department of Pediatric Cardiology, Guangdong Provincial Cardiovascular Institute, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510180, P.R. China.
authors.forename: Guo-Hong
authors.initials: GH
authors.lastname: Zeng
mesh_terms: D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007477:Ions / Q000633:toxicity; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009532:Nickel / Q000633:toxicity*; D059467:Transcriptome / Q000187:drug effects*
chemical_list: D007477:Ions; D009532:Nickel