85 An Approach to Test Effects on Secondary Organs via Lung Cells Exposed at the Air Liquid Interphase

• Published in: Annals of work exposures and health Vol. 67; no. Supplement_1; p. i58
• Main Authors: Mariussen, Espen, Skuland, Tonje, Dahlman, Hans Jørgen, Låg, Marit, Øvrevik, Johan
• Format: Journal Article
• Language: English
• Published: 10-05-2023
• ISSN: 2398-7308; 2398-7316
• DOI: 10.1093/annweh/wxac087.141

Abstract
Air pollutions are shown to increase the occurrence of cardiovascular diseases and ischemic stroke. These effects imply an indirect exposure of secondary organs downstream of the respiratory system as the primary target of exposure. Mechanistic studies of air pollution on secondary organs have traditionally been performed on organ specific monocultures at submerged conditions. Direct exposure to organ specific cells secondary exposed to air pollution have the drawback that it does not imply realistic exposure conditions. In this study we have indirectly exposed organ specific cells to particulate matter via exposure of a bronchial lung model at the air liquid interphase (ALI). The lung model was exposed to a model diesel particle (DEP) and an equivalent dose of an acetone extract of the DEP. The DEP induced induction of IL-6 formation of which the DEP was more potent than the DEP extract. The DEP extract inhibited CXCL8 formation, which appeared contradictory since both the DEP and DEP-extract increased expression of CXCL8 mRNA. Our results showed a substantial increased expression of CyP1A1 and CyP1B1 in both epithelial and endothelial cells in the lung model of which no differences were observed between the DEP and DEP-extract. However, the solvent extract induced the CYPs with a higher potency in the secondary exposed HepG2 liver cells, probably due to faster permeation of dissolved substances in the DEP extract through the lung barrier. Thus, organ specific cell models can be combined to achieve a more realistic so-called body-specific model to study secondary effects.