Perinatal exposure to tetrabromobisphenol A (TBBPA), a brominated flame retardant, exacerbated the pneumonia in respiratory syncytial virus (RSV)-infected offspring mice

Watanabe, Wataru; Hirose, Akihiko; Takeshita, Tomomi; Hashiguchi, Seiko; Sakata, Kentaro; Konno, Katsuhiko; Miyauchi, Aki; Akashi, Takumi; Yoshida, Hiroki; Sugita, Chihiro; Kurokawa, Mineo

doi:10.2131/jts.42.789

Cited by 11 publications

(8 citation statements)

References 17 publications

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“…The main marker used to monitor TBBPA effects on immune system is the production of cytokines. For example, this is the case of tumor necrosis factor alpha ( Tnf-α ), interferon γ ( Ifnγ ) or Il-4/6/8/24 ( Watanabe et al, 2010 , 2017 ; Koike et al, 2013 ; Park et al, 2014 ; Almughamsi and Whalen, 2016 ). In another study Wang et al ( Wang et al, 2019 ) found that macrophages exposed to TBBPA over-express pro-inflammatory cytokines ( Il-1β , Il-6 , and Tnf-α ), together with a reduced expression of antigen-presenting-related genes (including Cd86 , DE in our datasets).…”

Section: Discussionmentioning

confidence: 99%

Tetrabromobisphenol A effects on differentiating mouse embryonic stem cells reveals unexpected impact on immune system

2022

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Tetrabromobisphenol A (TBBPA) is a potent flame retardant used in numerous appliances and a major pollutant in households and ecosystems. In vertebrates, it was shown to affect neurodevelopment, the hypothalamic-pituitary-gonadal axis and thyroid signaling, but its toxicity and modes of actions are still a matter of debate. The molecular phenotype resulting from exposure to TBBPA is only poorly described, especially at the level of transcriptome reprogramming, which further limits our understanding of its molecular toxicity. In this work, we combined functional genomics and system biology to provide a system-wide description of the transcriptomic alterations induced by TBBPA acting on differentiating mESCs, and provide potential new toxicity markers. We found that TBBPA-induced transcriptome reprogramming affect a large collection of genes loosely connected within the network of biological pathways, indicating widespread interferences on biological processes. We also found two hotspots of action: at the level of neuronal differentiation markers, and surprisingly, at the level of immune system functions, which has been largely overlooked until now. This effect is particularly strong, as terminal differentiation markers of both myeloid and lymphoid lineages are strongly reduced: the membrane T cell receptor (Cd79a, Cd79b), interleukin seven receptor (Il7r), macrophages cytokine receptor (Csf1r), monocyte chemokine receptor (Ccr2). Also, the high affinity IgE receptor (Fcer1g), a key mediator of allergic reactions, is strongly induced. Thus, the molecular imbalance induce by TBBPA may be stronger than initially realized.

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Section: Discussionmentioning

confidence: 99%

Tetrabromobisphenol A effects on differentiating mouse embryonic stem cells reveals unexpected impact on immune system

2022

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“…DNA microarray analysis was performed as previously reported (Furuichi et al, 2011;Watanabe et al, 2017). Intensity values of each scanned feature were quantified using Agilent Feature Extraction software version 11.5.1.1, which performs background subtractions.…”

Section: Microarray Analysismentioning

confidence: 99%

Gene expression profiles in the dorsal root ganglia of methylmercury-exposed rats

et al. 2019

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Methylmercury (MeHg) exposure is known to induce neurodegeneration in both the central nervous system (CNS) and peripheral nervous system (PNS). Molecular mechanisms of MeHg-induced neurotoxicity have been well investigated in the CNS, however, it remains unclear in the PNS. In the present study, comprehensive gene expression analysis was performed by analyzing MeHg-exposed adult rat dorsal root ganglion (DRG) by DNA microarray. Methylmercuric chloride (6.7 mg/kg/day) was administered to nine-week-old male Wistar rats for five days, followed by two days without administration; this cycle was repeated once. Rats were anesthetized at 7 or 14 days after commencement of MeHg exposure, and their DRGs were removed and homogenized to make total RNA samples. DNA microarray data from Day 7 samples identified 100 out of 18,513 detected genes as annotated genes with more than two-fold upregulated or downregulated expression compared with controls. Database for Annotation, Visualization, and Integrated Discovery (DAVID) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses suggested strong involvement of immune activation and inflammation pathways in rat DRG exposed to MeHg, and some genes overlapped with previously reported genes affected by MeHg exposure in the cerebellum. The present results suggest that MeHg-induced neurotoxicity is associated with immune activation and inflammatory responses in rat DRG.

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“…Respiratory syncytial virus (RSV) causes pneumonia and bronchitis, mainly in infants, children, and elderly people with underlying diseases (Griffiths et al, 2017). In our previous research, we evaluated the effects of various nanomaterials and bacterial particles on the pathology of RSV pneumonia in mice, and investigated the toxicity and effects of these particles on the immune system (Watanabe et al, 2017;Miyauchi et al, 2019). In addition, we confirmed that intranasal administration of MWCNT to RSV-infected mice caused immune system cells in the bronchioles and alveoli to react to the carbon fibers and exacerbated RSV pneumonia (Hashiguchi et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Effects of inhalation of multi-walled carbon nanotube (MWCNT) on respiratory syncytial virus (RSV) infection in mice

Miyauchi

Akashi

Yokota³

et al. 2023

J. Toxicol. Sci.

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Multi-walled carbon nanotubes (MWCNTs), a kind of nanomaterial, are widely used in battery electrodes and composite materials, but the adverse effects associated with their accumulation in the living body have not been sufficiently investigated. MWCNTs are a fibrous material with molecules similar to asbestos fibers, and there are concerns about its effects on the respiratory system. In this study, we conducted a risk assessment by exposing mice using a previously developed nanomaterial inhalation exposure method. We quantified the exposure in the lungs by a lung burden test, evaluated the deterioration due to pneumonia using respiratory syncytial virus (RSV) infection, and measured inflammatory cytokines in bronchoalveolar lavage fluid (BALF). As a result, in the lung burden test, the amount of MWCNT in the lung increased according to the inhalation dose. In the RSV infection experiment, CCL3, CCL5, and TGF-β, which are indicators of inflammation and lung fibrosis, were elevated in the MWCNTexposed group. Histological examination revealed cells phagocytosing MWCNT fibers. These phagocytic cells were also seen during the recovery period from RSV infection. The present study found that MWC-NT remained in the lungs for about a month or more, suggesting that the fibers may continue to exert immunological effects on the respiratory system. Furthermore, the inhalation exposure method enabled the exposure of nanomaterials to the entire lung lobe, allowing a more detailed evaluation of the effects on the respiratory system.

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Perinatal exposure to tetrabromobisphenol A (TBBPA), a brominated flame retardant, exacerbated the pneumonia in respiratory syncytial virus (RSV)-infected offspring mice

Cited by 11 publications

References 17 publications

Tetrabromobisphenol A effects on differentiating mouse embryonic stem cells reveals unexpected impact on immune system

Tetrabromobisphenol A effects on differentiating mouse embryonic stem cells reveals unexpected impact on immune system

Gene expression profiles in the dorsal root ganglia of methylmercury-exposed rats

Effects of inhalation of multi-walled carbon nanotube (MWCNT) on respiratory syncytial virus (RSV) infection in mice

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