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Zimmermann, E. ; Candeias, J.* ; Gawlitta, N. ; Bisig, B. ; Binder, S. ; Pantzke, J. ; Offer, S. ; Rastak, N. ; Bauer, S. ; Huber, A.* ; Kühn, E.* ; Buters, J.* ; Gröger, T.M. ; Delaval, M.N. ; Oeder, S. ; Di Bucchianico, S. ; Zimmermann, R.

Biological impact of sequential exposures to allergens and ultrafine particles rich combustion aerosol on human bronchial epithelial BEAS-2B cells at the air liquid interface.

J. Appl. Toxicol. 43, 1225-1241 (2023)

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The prevalence of allergic diseases is constantly increasing since few decades. Anthropogenic ultrafine particles (UFP) and allergenic aerosols is highly involved in this increase, however the underlying cellular mechanisms are not yet understood. Studies observing these effects focused mainly on singular in vivo or in vitro exposures of single particle sources, while there is only limited evidence on their subsequent or combined effects. Our study aimed at evaluating the effect of subsequent exposures to allergy-related anthropogenic and biogenic aerosols on cellular mechanism exposed at air-liquid interface (ALI) conditions. Bronchial epithelial BEAS-2B cells were exposed to UFP-rich combustion aerosols for 2 h with or without allergen pre-exposure to birch pollen extract (BPE) or house dust mite extract (HDME). The physicochemical properties of the generated particles were characterized by state-of-the-art analytical instrumentation. We evaluated the cellular response in terms of cytotoxicity, oxidative stress, genotoxicity, and in-depth gene expression profiling. We observed that single exposures with UFP, BPE and HDME cause genotoxicity. Exposure to UFP induced pro-inflammatory canonical pathways, shifting to a more xenobiotic related response with longer pre-incubation time. With additional allergen exposure, the modulation of pro-inflammatory and xenobiotic signaling was more pronounced and appeared faster. Moreover, aryl hydrocarbon receptor (AhR) signaling activation showed to be an important feature of UFP toxicity, which was especially pronounced upon pre-exposure. In summary, we were able to demonstrate the importance of subsequent exposure studies to understand realistic exposure situations and to identify possible adjuvant allergic effects as well as the underlying molecular mechanisms.

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