Dataset Information

Air-Liquid Interface Exposure of Lung Epithelial Cells to Low Doses of Nanoparticles to Assess Pulmonary Adverse Effects.

ABSTRACT: Reliable and predictive in vitro assays for hazard assessments of manufactured nanomaterials (MNMs) are still limited. Specifically, exposure systems which more realistically recapitulate the physiological conditions in the lung are needed to predict pulmonary toxicity. To this end, air-liquid interface (ALI) systems have been developed in recent years which might be better suited than conventional submerged exposure assays. However, there is still a need for rigorous side-by-side comparisons of the results obtained with the two different exposure methods considering numerous parameters, such as different MNMs, cell culture models and read outs. In this study, human A549 lung epithelial cells and differentiated THP-1 macrophages were exposed under submerged conditions to two abundant types of MNMs i.e., ceria and titania nanoparticles (NPs). Membrane integrity, metabolic activity as well as pro-inflammatory responses were recorded. For comparison, A549 monocultures were also exposed at the ALI to the same MNMs. In the case of titania NPs, genotoxicity was also investigated. In general, cells were more sensitive at the ALI compared to under classical submerged conditions. Whereas ceria NPs triggered only moderate effects, titania NPs clearly initiated cytotoxicity, pro-inflammatory gene expression and genotoxicity. Interestingly, low doses of NPs deposited at the ALI were sufficient to drive adverse outcomes, as also documented in rodent experiments. Therefore, further development of ALI systems seems promising to refine, reduce or even replace acute pulmonary toxicity studies in animals.

SUBMITTER: Diabate S

PROVIDER: S-EPMC7823463 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Air-Liquid Interface Exposure of Lung Epithelial Cells to Low Doses of Nanoparticles to Assess Pulmonary Adverse Effects.

Diabaté Silvia S Armand Lucie L Murugadoss Sivakumar S Dilger Marco M Fritsch-Decker Susanne S Schlager Christoph C Béal David D Arnal Marie-Edith ME Biola-Clier Mathilde M Ambrose Selina S Mülhopt Sonja S Paur Hanns-Rudolf HR Lynch Iseult I Valsami-Jones Eugenia E Carriere Marie M Weiss Carsten C

Nanomaterials (Basel, Switzerland) 20201229 1

Reliable and predictive in vitro assays for hazard assessments of manufactured nanomaterials (MNMs) are still limited. Specifically, exposure systems which more realistically recapitulate the physiological conditions in the lung are needed to predict pulmonary toxicity. To this end, air-liquid interface (ALI) systems have been developed in recent years which might be better suited than conventional submerged exposure assays. However, there is still a need for rigorous side-by-side comparisons of ...[more]

PMID: 33383962

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Project description:BackgroundAcrolein is a major component of environmental pollutants, cigarette smoke, and is also formed by heating cooking oil. We evaluated the interstrain variability of response to subchronic inhalation exposure to acrolein among inbred mouse strains for inflammation, oxidative stress, and tissue injury responses. Furthermore, we studied the response to acrolein vapor in the lung mucosa model using human primary bronchial epithelial cells (PBEC) cultured at an air-liquid interface (ALI) to evaluate the findings of mouse studies.MethodsFemale 129S1/SvlmJ, A/J, BALB/cByJ, C3H/HeJ, C57BL/6J, DBA/2J, and FVB/NJ mice were exposed to 1 part per million (ppm) acrolein or filtered air for 11 weeks. Total cell counts and protein concentrations were measured in bronchoalveolar lavage (BAL) fluid to assess airway inflammation and membrane integrity. PBEC-ALI models were exposed to acrolein vapor (0.1 and 0.2 ppm) for 30 minutes. Gene expression of proinflammatory, oxidative stress, and tissue injury-repair markers was assessed (cut off: ≥2 folds; p < 0.05) in the lung models.ResultsTotal BAL cell numbers and protein concentrations remained unchanged following acrolein exposure in all mouse strains. BALB/cByJ, C57BL/6J, and 129S1/SvlmJ strains were the most affected with an increased expression of proinflammatory, oxidative stress, and/or tissue injury markers. DBA/2J, C3H/HeJ, A/J, and FVB/NJ were affected to a lesser extent. Both matrix metalloproteinase 9 (Mmp9) and tissue inhibitor of metalloproteinase 1 (Timp1) were upregulated in the strains DBA/2J, C3H/HeJ, and FVB/NJ indicating altered protease/antiprotease balance. Upregulation of lung interleukin- (IL-) 17b transcript in the susceptible strains led us to investigate the IL-17 pathway genes in the PBEC-ALI model. Acrolein exposure resulted in an increased expression of IL-17A, C, and D; IL-1B; IL-22; and RAR-related orphan receptor A in the PBEC-ALI model.ConclusionThe interstrain differences in response to subchronic acrolein exposure in mouse suggest a genetic predisposition. Altered expression of IL-17 pathway genes following acrolein exposure in the PBEC-ALI models indicates that it has a central role in chemical irritant toxicity. The findings also indicate that genetically determined differences in IL-17 signaling pathway genes in the different mouse strains may explain their susceptibility to different chemical irritants.

Project description:Due to its antibacterial properties, silver (Ag) has been used in more consumer products than any other nanomaterial so far. Despite the promising advantages posed by using Ag-nanoparticles (NPs), their interaction with mammalian systems is currently not fully understood. An exposure route via inhalation is of primary concern for humans in an occupational setting. Aim of this study was therefore to investigate the potential adverse effects of aerosolised Ag-NPs using a human epithelial airway barrier model composed of A549, monocyte derived macrophage and dendritic cells cultured in vitro at the air-liquid interface. Cell cultures were exposed to 20 nm citrate-coated Ag-NPs with a deposition of 30 and 278 ng/cm2 respectively and incubated for 4 h and 24 h. To elucidate whether any effects of Ag-NPs are due to ionic effects, Ag-Nitrate (AgNO3) solutions were aerosolised at the same molecular mass concentrations.Agglomerates of Ag-NPs were detected at 24 h post exposure in vesicular structures inside cells but the cellular integrity was not impaired upon Ag-NP exposures. Minimal cytotoxicity, by measuring the release of lactate dehydrogenase, could only be detected following a higher concentrated AgNO3-solution. A release of pro-inflammatory markers TNF-? and IL-8 was neither observed upon Ag-NP and AgNO3 exposures as well as was not affected when cells were pre-stimulated with lipopolysaccharide (LPS). Also, an induction of mRNA expression of TNF-? and IL-8, could only be observed for the highest AgNO3 concentration alone or even significantly increased when pre-stimulated with LPS after 4 h. However, this effect disappeared after 24 h. Furthermore, oxidative stress markers (HMOX-1, SOD-1) were expressed after 4 h in a concentration dependent manner following AgNO3 exposures only.With an experimental setup reflecting physiological exposure conditions in the human lung more realistic, the present study indicates that Ag-NPs do not cause adverse effects and cells were only sensitive to high Ag-ion concentrations. Chronic exposure scenarios however, are needed to reveal further insight into the fate of Ag-NPs after deposition and cell interactions.

Dataset Information

Air-Liquid Interface Exposure of Lung Epithelial Cells to Low Doses of Nanoparticles to Assess Pulmonary Adverse Effects.

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Air-Liquid Interface Exposure of Lung Epithelial Cells to Low Doses of Nanoparticles to Assess Pulmonary Adverse Effects.

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