INTERACTIONS BETWEEN HUMAN BRONCHOEPITHELIAL CELLS AND LUNG FIBROBLASTS AFTER OZONE EXPOSURE IN-VITRO

Long-term exposure to ozone has been shown to cause lung fibrosis and increased collagen synthesis by fibroblasts in experimental animals. A s the bronchial epithelium appears to play a major regulatory role in inflammatory processes, we investigated whether ozone induces bronchoe pithelial cells in vitro to increase gene expression of procollagens a nd other fibrogenic mediators in human lung fibroblasts. Membrane cult ures of human airway epithelial cells (BEAS-2B) in the presence or abs ence of lung fibroblast (HFL-I) cultures were exposed to air or 500 pp b ozone for 1 h, followed by (co-)incubation periods of 11 and 23 h. A fter ozone exposure of the co-cultures, there were substantial increas es of steady-state mRNA levels of both alpha(1) procollagens type I an d III as well as TGF beta(1) in the fibroblasts above the correspondin g air control levels. In the absence of ozone, the presence of epithel ial cells always caused significant decreases in the basal steady-stat e mRNA levels of both procollagens as compared to their absence. There were no significant effects of ozone on the secretion or gene express ion of TGF beta(2), PDGF or IL-8 in any cell type. In contrast, co-cul ture condition induced altered patterns of IL-8 gene expression or of PDGF production in fibroblasts and bronchoepithelial cells, respective ly, both in the absence or presence of ozone. In summary, our data dem onstrate that the effect of ozone on fibroblasts was mediated by epith elial cells and that mutual regulatory interactions between the differ ent cell types occur. Thus, our co-cultivation system in vitro appears to be able to mimic the in vivo situation providing insight into the nature of cellular interactions and modulation by ozone, which may occ ur in the whole organism after long-term exposure. (C) 1998 Elsevier S cience Ireland Ltd. All rights reserved.