Particulate Matter Decreases Intestinal Barrier-Associated Proteins Levels in 3D Human Intestinal Model

Brittany Woodby, Maria Lucia Schiavone, Erika Pambianchi, Angela Mastaloudis, Shelly N. Hester, Steven M. Wood, Alessandra Pecorelli and Giuseppe Valacchi

Background: The gastrointestinal tract (GI) tract is one of the main organs exposed to particulate matter (PM) directly through ingestion of contaminated food or indirectly through inhalation. Previous studies have investigated the effects of chronic PM exposure on intestinal epithelia in vitro using Caco−2 cells and in vivo using mice. In this study, we hypothesized that chronic PM exposure would increase epithelial permeability and decrease barrier function due to altered redox homeostasis, which alters levels and/or localization of barrier-associated proteins in human three-dimensional (3D) intestinal tissues. (2) Methods: Transepithelial electrical resistance (TEER) in tissues exposed to 50, 100, 150, 250, and 500 µg/cm2 of PM for 1 week and 2 weeks was analyzed. Levels and localization of tight junction proteins zonula occludens protein 1 (ZO−1) and claudin−1 and desmosome-associated desmocollin were analyzed using immunofluorescence. As a marker of oxidative stress, levels of 4-hydroxy-nonenal (4HNE) adducts were measured. (3) Results: No differences in TEER measurements were observed between exposed and un-exposed tissues. However, increased levels of 4HNE adducts in exposed tissues were observed. Additionally, decreased levels of ZO−1, claudin−1, and desmocollin were demonstrated. (4) Conclusion: These data suggest that chronic PM exposure results in an increase of oxidative stress; modified levels of barrier-associated proteins could possibly link to GI tract inflammatory conditions.


EpiIntestinal (SMI-100), Urban particulate matter, Tight Junction Proteins, TEER, ZO-1, claudin-1, desmocollin, oxidative stress, 4-hydroxynonenal (4HNE), Caco-2, gastrointestinal disorders

Materials Tested

standard reference material (SRM) 1648a, Urban particulate matter

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