Toxicity of nickel ions and comprehensive analysis of nickel ion-associated gene expression profiles in THP-1 cells.

The aim of the present study was to explore the toxic effects and underlying mechanisms of nickel ions during therapeutic nickel­based alloy­treatment in congenital heart disease by investigating the metal­induced cytotoxicity to the human monocyte­derived macrophage cell line THP­1. THP­1 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 THP­1 cell proliferation following NiCl2 treatment. Apoptosis of THP­1 cells was quantified using flow cytometry. Illumina sequencing was used for screening the associated genes, whose mRNA expression levels were further confirmed by quantitative real­time 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 (25­400 µM) for 48 h reduced cell viability in a dose­dependent manner. The mRNA expression levels of RELB, FIGF, SPI­1, CXCL16 and CRLF2 were significantly increased following nickel treatment. The results of the present study suggested that nickel ions exert toxic effects on THP­1 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 THP­1 cells (EPOR, RELB, FIGF, SPI­1, TGF­ß1, CXCL16 and CRLF2) may aid in the development of interventional measures for the treatment/prevention of nickel ion­associated toxic effects during the treatment of congenital heart disease.