title: Cis-bifenthrin causes immunotoxicity in murine macrophages.
abstract: Synthetic pyrethroids (SPs) are commonly used insecticides that have been detected in mammals, including humans, indicating a potential threat to human health. Bifenthrin (BF), as well as other pyrethroids, has been shown to possess neurotoxic, reproductive, hepatotoxic and nephrotoxic potential in mammals. However, studies regarding the immunotoxicity of BF and its mechanism are limited. In this study, we aim to exam the immunotoxicity of cis-BF on the murine macrophage cell line, RAW 264.7. MTT assay results demonstrated that cis-BF exposure induced apoptosis in RAW 264.7 cells in a concentration-dependent manner. We found that the expression of p53 and caspase-3 was up-regulated, while the expression of Bcl-2 was down-regulated during cis-BF-induced apoptosis. In addition, we also found that cis-BF exposure caused oxidative stress in RAW 264.7 cells in a dose-dependent manner. Interestingly, cis-BF exposure was found to inhibit the increase in transcription levels of IL-1β, IL-6 and TNF-α responding to LPS stimulation. We also found that the induced increase in IFN-β mRNA levels upon Sendai virus infection was blocked with cis-BF exposure. Finally, we found that cis-BF exposure increased ROS levels and dysregulated mRNA levels of oxidative stress-related genes in RAW 264.7 cells. The present study elucidates the immunotoxicity effect of cis-BF on macrophages and its possible underlying mechanism. The results from this study support the necessity to evaluate immune dysfunction in the risk assessment of cis-BF exposure.
authors.affiliation: College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Wang
authors.affiliation: College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, China.
authors.forename: Xingli
authors.initials: X
authors.lastname: Gao
authors.affiliation: College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, China.
authors.forename: Bingnan
authors.initials: B
authors.lastname: He
authors.affiliation: College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, China.
authors.forename: Yuanxiang
authors.initials: Y
authors.lastname: Jin
authors.affiliation: College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, China. Electronic address: azwfu@zjut.edu.cn.
authors.forename: Zhengwei
authors.initials: Z
authors.lastname: Fu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000235:genetics; D016207:Cytokines / Q000235:genetics; D007306:Insecticides / Q000633:toxicity*; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D011722:Pyrethrins / Q000633:toxicity*; D000067996:RAW 264.7 Cells; D017382:Reactive Oxygen Species / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: D016207:Cytokines; D007306:Insecticides; D019253:Proto-Oncogene Proteins c-bcl-2; D011722:Pyrethrins; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; C099952:bifenthrin; D053148:Caspase 3
keywords: Cis-bifenthrin; Immunotoxicity; Mechanism; Pyrethroids; RAW 264.7 cells