Small silica nanoparticles transiently modulate the intestinal permeability by actin cytoskeleton disruption in both Caco-2 and Caco-2/HT29-MTX models

Cornu, Raphaël; Chrétien, Chloé; Pellequer, Yann; Martin, Hélène; Béduneau, Arnaud

doi:10.1007/s00204-020-02694-6

Cited by 42 publications

(20 citation statements)

References 30 publications

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“…ZnONPs also significantly decreased claudin-5 expression level (Figure 4). Interestingly, a recent study showed that small silica nanoparticles modulate the epithelial paracellular barrier via impairing the stability of tight junction network [25]. Together, it is tempting to speculate that tight junctions might be a common target of nanoparticles.…”

Section: Discussionmentioning

confidence: 99%

Exposure to Zinc Oxide Nanoparticles Disrupts Endothelial Tight and Adherens Junctions and Induces Pulmonary Inflammatory Cell Infiltration

Chen

et al. 2020

IJMS

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Zinc oxide nanoparticles (ZnONPs) are frequently encountered nanomaterials in our daily lives. Despite the benefits of ZnONPs in a variety of applications, many studies have shown potential health hazards of exposure to ZnONPs. We have shown that oropharyngeal aspiration of ZnONPs in mice increases lung inflammation. However, the detailed mechanisms underlying pulmonary inflammatory cell infiltration remain to be elucidated. Endothelium functions as a barrier between the blood stream and the blood vessel wall. Endothelial barrier dysfunction may increase infiltration of immune cells into the vessel wall and underlying tissues. This current study examined the effects of ZnONPs exposure on endothelial barriers. ZnONPs exposure increased leukocyte infiltration in the mouse lungs. In endothelial cells, ZnONPs reduced the continuity of tight junction proteins claudin-5 and zonula occludens-1 (ZO-1) at the cell junctions. ZnONPs induced adherens junction protein VE-cadherin internalization from membrane to cytosol and dissociation with β-catenin, leading to reduced and diffused staining of VE-cadherin and β-catenin at cell junctions. Our results demonstrated that ZnONPs disrupted both tight and adherens junctions, compromising the integrity and stability of the junction network, leading to inflammatory cell infiltration. Thus, ZnONPs exposure in many different settings should be carefully evaluated for vascular effects and subsequent health impacts.

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Section: Discussionmentioning

confidence: 99%

Exposure to Zinc Oxide Nanoparticles Disrupts Endothelial Tight and Adherens Junctions and Induces Pulmonary Inflammatory Cell Infiltration

Chen

et al. 2020

IJMS

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“…In our study, all investigated SAS materials did not affect cell viability/metabolic activity of the intestinal co-cultures after exposure up to 50 µg/ml for 48 h. Similarly, the particle control PS-amine, which induced a slight cytotoxic response in differentiated Caco-2 monocultures (Hempt et al 2020 ), did not decrease cell viability in the co-cultures, presumably due to the presence of a protective mucus layer. A decreased sensitivity in regards of cell viability and barrier integrity has previously been reported for other nanomaterials including silver, SiO 2 and CuO nanoparticles when comparing the results of a Caco-2 monoculture with an intestinal co-culture model (Cornu et al 2020 ; Saez-Tenorio et al 2019 ; Ude et al 2019 , 2017 ; Vila et al 2018 ). However, a recent study found a considerable dose-dependent decrease in the viability/metabolic activity (PrestoBlue™ viability assay) of intestinal co-cultures treated with a food-grade SAS material (AEROSIL ® 200 F) compared to the Caco-2 monoculture (Sohal et al 2020 ).…”

Section: Discussionmentioning

confidence: 84%

Investigating the effects of differently produced synthetic amorphous silica (E 551) on the integrity and functionality of the human intestinal barrier using an advanced in vitro co-culture model

et al. 2020

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E 551, also known as synthetic amorphous silica (SAS), is the second most produced food additive. However, according to the re-evaluation of E 551 by the European Food Safety Authority (EFSA) in 2018, the amount of available data on the oral toxicity of food grade E 551 is still insufficient for reliable risk assessment. To close this gap, this study aimed to investigate six food-grade SAS with distinct physicochemical properties on their interaction with the intestinal barrier using advanced in vitro intestinal co-cultures and to identify potential structure–activity relationships. A mucus-secreting Caco-2/HT-29/Raji co-culture model was treated with up to 50 µg/ml SAS for 48 h, which represents a dose range relevant to dietary exposure. No effects on cell viability, barrier integrity, microvilli function or the release of inflammatory cytokine were detected after acute exposure. Slight biological responses were observed for few SAS materials on iron uptake and gene expression levels of mucin 1 and G-protein coupled receptor 120 (GPR120). There was no clear correlation between SAS properties (single or combined) and the observed biological responses. Overall, this study provides novel insights into the short-term impact of food-relevant SAS with distinct characteristics on the intestinal epithelium including a range of intestine-specific functional endpoints. In addition, it highlights the importance of using advanced intestinal co-cultures embracing relevant cell types as well as a protective mucus barrier to achieve a comprehensive understanding of the biological response of food additives at the intestinal barrier in vitro.

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“…One thing to consider when applying this assay is that cytoskeleton disruption may occur when cells are exposed to nanoparticles, depending on the physicochemical properties, size, and exposure time [ 35 , 36 ]. For this reason, the choice of nanoparticle and experimental conditions such as concentration should be optimized.…”

Section: Resultsmentioning

confidence: 99%

Probing TGF-β1-induced cytoskeletal rearrangement by fluorescent-labeled silica nanoparticle uptake assay

Shin

Choi

Lee

2021

Biochemistry and Biophysics Reports

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Cytoskeletal proteins are essential in maintaining cell morphology, proliferation, and viability as well as internalizing molecules in phagocytic and non-phagocytic cells. Orderly aligned cytoskeletons are disturbed by a range of biological processes, such as the epithelial–mesenchymal transition, which is observed in cancer metastasis. Although many biological methods have been developed to detect cytoskeletal rearrangement, simple and quantitative in vitro approaches are still in great demand. Herein, we applied a flow cytometry-based nanoparticle uptake assay to measure the degree of cytoskeletal rearrangement induced by transforming growth factor β1 (TGF-β1). For the assay, silica nanoparticles, selected for their high biocompatibility, were fluorescent-labeled to facilitate quantification with flow cytometry. Human keratinocyte HaCaT cells were treated with different concentrations of TGF-β1 and then exposed to FITC-labeled silica nanoparticles. Increasing concentrations of TGF-β1 induced gradual changes in cytoskeletal rearrangement, as confirmed by conventional assays. The level of nanoparticle uptake increased by TGF-β1 treatment in a dose-dependent manner, indicating that our nanoparticle uptake assay can be used as a quick and non-destructive approach to measure cytoskeletal rearrangement.

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Small silica nanoparticles transiently modulate the intestinal permeability by actin cytoskeleton disruption in both Caco-2 and Caco-2/HT29-MTX models

Cited by 42 publications

References 30 publications

Exposure to Zinc Oxide Nanoparticles Disrupts Endothelial Tight and Adherens Junctions and Induces Pulmonary Inflammatory Cell Infiltration

Exposure to Zinc Oxide Nanoparticles Disrupts Endothelial Tight and Adherens Junctions and Induces Pulmonary Inflammatory Cell Infiltration

Investigating the effects of differently produced synthetic amorphous silica (E 551) on the integrity and functionality of the human intestinal barrier using an advanced in vitro co-culture model

Probing TGF-β1-induced cytoskeletal rearrangement by fluorescent-labeled silica nanoparticle uptake assay

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