Effects of Acute Low-Dose Exposure to the Chlorinated Flame Retardant Dechlorane 602 and Th1 and Th2 Immune Responses in Adult Male Mice

Yu, Feng; Tian, Jianhui; Xie, Heidi Qunhui; She, Jianwen; Xu, Sherry Li; Xu, Tuan; Tian, Wenjing; Fu, Hualing; Li, Shuaizhang; Tao, Wuqun; Wang, Lingyun; Chen, Yangsheng; Zhang, Songyan; Ding, Ning; Guo, Tai L.; Zhao, Bin

doi:10.1289/ehp.1510314

Cited by 24 publications

(23 citation statements)

References 34 publications

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“…A similar effect was observed when the exposure of mice to HgS showed no effect on spleen and thymus weight while it changed the mRNA levels of cytokines in these two immune organs . Additionally, the exposure of mice to the chlorinated flame retardant Dechlorane 602 caused no notable histological change in the spleen, while it changed the mRNA levels of IL‐4 , IL‐10 , and IL‐13 in the spleen . In addition, xenobiotics usually show dose‐dependent toxic effects in organisms.…”

Section: Discussionsupporting

confidence: 57%

8:2 Fluorotelomer alcohol causes immunotoxicity and liver injury in adult male C57BL/6 mice

Wang

Kong

et al. 2018

Environmental Toxicology

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8:2 Fluorotelomer alcohol (8:2 FTOH) is widely used in houseware and industrial goods and is ubiquitous in the surrounding environment. 8:2 FTOH has been linked to hepatoxicity, nephrotoxicity, and reproductive toxicity, as well as endocrine-disrupting effects. However, as of yet, the research regarding immunotoxicity of 8:2 FTOH remains largely limited. In the present study, adult male C57BL/6 mice were administered with 10, 30, and 100 mg/kg/d 8:2 FTOH by gavage for 28 days to investigate its immunotoxicity in vivo. The results showed that exposure to 8:2 FTOH caused increases in liver weight and histological changes in the liver, including vacuolation, cell swelling, immune cell infiltration, karyopyknosis and nuclear swelling. No histological change in either the spleen or the thymus was observed after administration of 8:2 FTOH. In addition, exposure to 8:2 FTOH reduced the concentration of IL-1β in serum, and mRNA levels of IL-1β, IL-6, and TNF-α in both the thymus and spleen. CXCL-1 mRNA expression was downregulated in both the liver and thymus after 8:2 FTOH administration, while only IL-1β mRNA expression was upregulated in the liver. Moreover, the exposure of primary cultured splenocytes to 8:2 FTOH inhibited the ConA-stimulated proliferation of splenocytes at concentrations of 30 and 100 μM, and the LPS-stimulated proliferation of splenocytes at 100 μM. Furthermore, 8:2 FTOH inhibited the level of secreted IFN-γ in ConA-stimulated splenocytes. The results obtained in the study demonstrated that 8:2 FTOH posed potential immunotoxicity and liver injury in mice. Our findings will provide novel data for the health risk assessment of 8:2 FTOH. K E Y W O R D S 8:2 FTOH, immunotoxicity, liver injury, mice, oxidative stress 1 | INTRODUCTION Fluorotelomers, as fluorocarbon-based oligomers or telomers, have various applications in food packaging, home furnishings, fire-fighting foams, surfactants, textiles, adhesives, waxes, polishes, and leather. 1 It was reported that the market size of fluorotelomers was 26.5 kt in 2015, and its annual growth rate is estimated to be 12.7%. 2 Among fluorotelomers, fluorotelomer alcohol (FTOH) products dominate global consumption; these products reportedly made up approximately 32% of the overall volume of fluorotemomers in 2013. 3 8:2 FTOH is the most abundant FTOH homologue and is ubiquitous in the environment. 4 Chen et al. 5 detected FTOHs in several wastewater treatment plants in China, and the study also found that 8:2 FTOH was the primary FTOH in the influent, secondary effluent, and sludge, with the concentrations ranging from 2.10 to 11.0 ng/L, 3.05 to 12.4 ng/L, and 0.36 to 1.91 ng/g dry weight, respectively. Bach et al. 6 assessed 14 perfluorinated compounds (PFCs) in water samples in France and found that the concentrations of 8:2 FTOH were 117 ng/L and 213 ng/L in tap and surface water, respectively. Additionally, 8:2 FTOH was commonly detected in food contact materials (FCMs). For example, 8:2 FTOH was detected in most Chinese and American FCM samples at concentra...

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Section: Discussionsupporting

confidence: 57%

8:2 Fluorotelomer alcohol causes immunotoxicity and liver injury in adult male C57BL/6 mice

Wang

Kong

et al. 2018

Environmental Toxicology

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“…Each subpopulation is characterized by unique transcription factors and cytokine patterns. CD4 + Th lymphocytes can be divided into Th1 (IFN-γ, IL-2 and TNF-α) and Th2 (IL-4, IL-5, IL-6, IL-10 and IL-13) subsets on the basis of their cytokine secretion profile [73–75]. Th1 cytokines induce the cell-mediated immune response targeted against intracellular pathogens [76].…”

Section: Discussionmentioning

confidence: 99%

“…Th1 cytokines induce the cell-mediated immune response targeted against intracellular pathogens [76]. They promote isotype class switching to produce IgG2 [73, 77] and they trigger antibody-dependent cellular cytotoxicity. Th2 cytokines induce powerful antibody-mediated responses [78].…”

Section: Discussionmentioning

confidence: 99%

Immunomodulatory effects of Rhipicephalus haemaphysaloides serpin RHS2 on host immune responses

Wang

Wei

et al. 2019

Parasites Vectors

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Background Rhipicephalus haemaphysaloides is a widespread tick species in China and other South East Asian countries, where it is the vector of many pathogens. The objective of this study was to study the role of serpin (serine protease inhibitor) during the tick-host interaction. Methods The differentiation of bone marrow-derived dendritic cells (BMDC) was induced in vitro , and the effect of RHS2 on the maturation of DCs was evaluated. The effects of RHS2 on T cell activation and cytotoxic T lymphocytes’ (CTLs) activity were analyzed by flow cytometry. Antibody subtypes after immunization of mice with RHS2 and OVA were determined. Results RHS2 can inhibit the differentiation of bone marrow-derived cells into DCs and promote their differentiation into macrophages. RHS2 can inhibit the maturation of DCs and the expression of CD80, CD86 and MHCII. The number of CD3 + CD4 + and CD3 + CD8 + T cells secreting IFN-γ, IL-2 and TNF-α was decreased, and the number of CD3 + CD4 + T cells secreting IL-4 was increased, indicating that RHS2 can inhibit the activation of CD4 T cells and CD8 T cells, leading to inhibition of Th1 immune response. RHS2 inhibits the elimination of target cells by cytotoxic T lymphocytes. After immunization of mice with RHS2 and OVA, serum IgG2b was significantly reduced and IgM was increased. Conclusions The results show that RHS2 has an inhibitory effect on the host immune response. Ticks have evolved various ways to circumvent adaptive immunity. Their serpin inhibits BMDC differentiation to reduce immune responses.

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“…T-bet and ROR-γt are key transcription factors for Th1 and Th17 cells respectively. The expression levels of these transcription factors are associated with the release of proinflammatory cytokines, including IFN-γ, IL-17A, and so on (Chen et al, 2016 ; Feng et al, 2016 ). T-bet is also necessary for EAE development, as T-bet −/− mice are resistant to EAE (Bettelli et al, 2004 ).…”

Section: Discussionmentioning

confidence: 99%

Pien Tze Huang Alleviates Relapsing-Remitting Experimental Autoimmune Encephalomyelitis Mice by Regulating Th1 and Th17 Cells

Qiu

Guo

et al. 2018

Front. Pharmacol.

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Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS), characterized by infiltrating inflammatory cells and demyelinating lesions, and T helper (Th) cells play critical roles in the pathogenesis of MS. There is still lack of effective treatments currently. Pien Tze Huang (PZH), a traditional Chinese medicine formula, has been proved to have anti-inflammatory, neuroprotective, and immunoregulatory effects. However, whether PZH can be used to treat MS is still obscure. This study aimed to investigate the possible therapeutic effect and the underlying action mechanism of PZH in relapsing-remitting experimental autoimmune encephalomyelitis (RR-EAE) mice. Female SJL/J mice were immunized with myelin proteolipid protein 139–151 (PLP139−151) and pertussis toxin to establish RR-EAE model. Mice were then randomly divided into normal group, model group, PZH group and positive control group (fingolimod, FTY-720), and drugs were orally administered for 60 days from the day 10 after immunization. Sera of mice were collected for ELISA detection. Tissues of CNS were harvested for hematoxylin-eosin (H-E) and luxol fast blue (LFB) staining. Furthermore, Th1, Th17 cells and their related cytokines in the CNS were detected by flow cytometry and quantitative real-time PCR, respectively. Proteins involved in STAT and NF-κB signaling pathways were detected by western blot. The results showed that PZH-treated mice displayed mild or moderate clinical symptoms compared with untreated EAE mice that exhibited severe clinical symptoms. PZH remarkably reduced inflammatory cell infiltration and myelin damage in the CNS of EAE mice. It markedly down-regulated the levels of IFN-γ and IL-17A in sera of EAE mice. Moreover, PZH could reduce the percentages of Th1 and Th17 cells. It also suppressed the production of transcription factors ROR-γt and T-bet as well as the mRNA levels of their downstream pro-inflammatory cytokines, such as IFN-γ and IL-17A. Furthermore, PZH could inhibit the phosphorylation of some key proteins in the STAT and NF-κB signaling pathways. In conclusion, the study demonstrated that PZH had a therapeutic effect on RR-EAE mice, which was associated with the modulation effect on Th1 and Th17 cells.

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Effects of Acute Low-Dose Exposure to the Chlorinated Flame Retardant Dechlorane 602 and Th1 and Th2 Immune Responses in Adult Male Mice

Cited by 24 publications

References 34 publications

8:2 Fluorotelomer alcohol causes immunotoxicity and liver injury in adult male C57BL/6 mice

8:2 Fluorotelomer alcohol causes immunotoxicity and liver injury in adult male C57BL/6 mice

Immunomodulatory effects of Rhipicephalus haemaphysaloides serpin RHS2 on host immune responses

Pien Tze Huang Alleviates Relapsing-Remitting Experimental Autoimmune Encephalomyelitis Mice by Regulating Th1 and Th17 Cells

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