title: A multivariate assessment of innate immune-related gene expressions due to exposure to low concentration individual and mixtures of four kinds of heavy metals on zebrafish (Danio rerio) embryos.
abstract: Concerns over the potential health effects of mixtures of low concentration heavy metals on living organisms keep growing by the day. However, the toxicity of low concentration metal mixtures on the immune system of fish species has rarely been investigated. In this study, the zebrafish model was employed to investigate the effect on innate immune and antioxidant-related gene expressions, on exposure to environmentally relevant concentrations of individual and mixtures of Pb (0.01 mg/L), Hg (0.001 mg/L), As (0.01 mg/L) and Cd (0.005 mg/L). Messenger-RNA (mRNA) levels of IL1β, TNF-α, IFNγ, Mx, Lyz, C3B and CXCL-Clc which are closely associated with the innate immune system were affected after exposing zebrafish embryos to metals for 120 h post fertilization (hpf). Individual and mixtures of metals exhibited different potentials to modulate innate-immune gene transcription. IL1β genes were significantly up regulated on exposure to Pb + As (2.01-fold) and inhibited on exposure to Pb + Hg + Cd (0.13-fold). TNF-α was significantly inhibited on exposure to As (0.40-fold) and Pb + As (0.32-fold) compared to control. Metal mixtures generally up regulated IFNγ compared to individual metals. Additionally, antioxidant genes were affected, as CAT and GPx gene expressions generally increased, whiles Mn-SOD and Zn/Cu-SOD reduced. Multivariate analysis showed that exposure to individual metals greatly influenced modulation of innate immune genes; whiles metal mixtures influenced antioxidant gene expressions. This suggests that beside oxidative stress, there may be other pathways influencing gene expressions of innate immune and antioxidant-related genes. Low concentration heavy metals also affect expression of development-related (wnt8a and vegf) genes. Altogether, the results of this study clearly demonstrate that low concentration individual and mixtures of metals in aquatic systems will greatly influence the immune system. It is indicative that mechanisms associated with toxicity of metal mixtures is complex, however, further studies to elucidate them are ongoing in our research laboratory.
authors.affiliation: School of the Environment and Safety Engineering, Jiangsu University, Xuefu Rd. 301, Zhenjiang 212013, Jiangsu, China.
authors.forename: Samuel Jerry
authors.initials: SJ
authors.lastname: Cobbina
authors.affiliation: School of the Environment and Safety Engineering, Jiangsu University, Xuefu Rd. 301, Zhenjiang 212013, Jiangsu, China.
authors.forename: Hai
authors.initials: H
authors.lastname: Xu
authors.affiliation: School of Chemistry and Chemical Engineering, Jiangsu University, Xuefu Rd. 301, Zhenjiang 212013, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Zhao
authors.affiliation: School of the Environment and Safety Engineering, Jiangsu University, Xuefu Rd. 301, Zhenjiang 212013, Jiangsu, China.
authors.forename: Guanghua
authors.initials: G
authors.lastname: Mao
authors.affiliation: School of Chemistry and Chemical Engineering, Jiangsu University, Xuefu Rd. 301, Zhenjiang 212013, China.
authors.forename: Zhaoxiang
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: School of Chemistry and Chemical Engineering, Jiangsu University, Xuefu Rd. 301, Zhenjiang 212013, China.
authors.forename: Xueshan
authors.initials: X
authors.lastname: Wu
authors.affiliation: School of the Environment and Safety Engineering, Jiangsu University, Xuefu Rd. 301, Zhenjiang 212013, Jiangsu, China.
authors.forename: Hongyang
authors.initials: H
authors.lastname: Liu
authors.affiliation: School of the Environment and Safety Engineering, Jiangsu University, Xuefu Rd. 301, Zhenjiang 212013, Jiangsu, China.
authors.forename: Yanmin
authors.initials: Y
authors.lastname: Zou
authors.affiliation: School of the Environment and Safety Engineering, Jiangsu University, Xuefu Rd. 301, Zhenjiang 212013, Jiangsu, China. Electronic address: wuxy@ujs.edu.cn.
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Wu
authors.affiliation: School of Chemistry and Chemical Engineering, Jiangsu University, Xuefu Rd. 301, Zhenjiang 212013, China. Electronic address: yangliuqing@ujs.edu.cn.
authors.forename: Liuqing
authors.initials: L
authors.lastname: Yang
mesh_terms: D000818:Animals; D029941:Fish Proteins / Q000235:genetics* / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D007113:Immunity, Innate; D019216:Metals, Heavy / Q000633:toxicity*; D015999:Multivariate Analysis; D011897:Random Allocation; D014874:Water Pollutants, Chemical / Q000633:toxicity*; D015027:Zebrafish / Q000235:genetics* / Q000276:immunology / Q000378:metabolism
chemical_list: D029941:Fish Proteins; D019216:Metals, Heavy; D014874:Water Pollutants, Chemical
keywords: Cytokines; Embryonic exposure; Innate immune; Low concentration; Metal mixtures; Multivariate analysis; Zebra fish