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Growth of airway epithelial cells at an air-liquid interface changes both the response to particle exposure and iron homeostasis
Citation:
GHIO, A. J., L. A. DAILEY, J. M. SOUKUP, J. STONEHUERNER, J. E. RICHARDS, A. Ross, AND R. B. DEVLIN. Growth of airway epithelial cells at an air-liquid interface changes both the response to particle exposure and iron homeostasis. TOXICOLOGY AND APPLIED PHARMACOLOGY. Academic Press Incorporated, Orlando, FL.
Impact/Purpose:
This is an article demonstrating that cells allowed to differentiate at an air-liquid interface show less response to air pollution particles.
Description:
We tested the hypothesis that 1) relative to submerged cells, airway epithelial cells grown at an air-liquid interface and allowed to differentiate would have an altered response to particle exposure and 2) that these differences would be associated with indices of iron homeostasis. RNA for IL-8, IL-6, heme oxygenase 1 and cyclooxygenase 2 increased following exposures of submerged airway epithelial cells to ambient air pollution particle. The same cells allowed to differentiate at an air-liquid interface demonstrated no such changes following particle exposure. Airway epithelial cells showed no changes in iron, ferritin, and divalent metal transporter 1 (DMTl) when grown submerged in media. In contrast, these three indices of iron homeostasis increased in cells grown at an air-liquid interface. To test for an association between changes in iron homeostasis with senescence and altered sensitivity to particle exposure, older rats were used in studies. Relative to 2 month old animals, those animals 18 months old demonstrated a decreased biological effect of particle exposure. Older animals had elevated concentrations of liver and lung non-heme iron and higher serum ferritin values. Qualitative differences in DMTI were observed with increased expression of this transport protein in the aged animals. We conclude that growth of airway epithelial cells at an air-liquid interface is associated with a diminished biological effect following particle exposure. This decreased response was not related to differentiation but corresponded to changes in iron homeostasis. Older rats similarly demonstrated increased levels of iron and iron-related proteins and a diminished biological response to particles