Research Program Area: Health & Exposure
The concern that environmental exposure to ozone may cause fibrotic remodeling of terminal airways is difficult to address experimentally in human volunteers because long term experimental exposures to ozone are difficult to carry out, and direct objective measures of lung fibrosis in living subjects are not currently possible. Despite these difficulties, it is possible to make indirect assessment of the potential for inhaled materials to provoke fibrosis in the lungs. One such method is to determine if airway and alveolar lining fluid collected at bronchoalveolar lavage (BAL) after exposure to ozone causes increased activity of cultured human lung fibroblasts (the specialized cells that are the exclusive source of collagen, and thus of fibrosis). Fibroblast activity can be measured by recording the extent of incorporation of radio-labelled thymidine - a component of cellular DNA. Thus, the principal goal of this work was to determine if brief exposure of human subjects to ozone in an environmental chamber results in increased fibroblast stimulating activity (FSA) of BAL. In addition, we measured transforming growth factors 1 & 2 (TGFb1 & TGFb2) in the BAL samples. TGFb1 and TGFb2 are proteins implicated as mediators of fibrosis in a variety of organ systems, including the lung. During two visits separated by 4 weeks, we exposed subjects to air and to ozone (0.4 ppm) for 3 hours while they performed intermittent moderate exercise. BAL was performed either within 1 hour (n=6) or between 16 and 18 hours of exposure (n=6). We found no significant difference in the FSA of the BAL or in the levels of TGFb1 in the BAL collected at the two time periods after ozone and air exposures. However, we found that the levels of TGFb2 were significantly higher in the BAL collected after the ozone exposures at both time points. Messenger RNA for TGFb1 and TGFb2 was found in the cell pellet of some but not all BAL samples, and ozone exposure did not influence the detection of these messenger RNAs. We conclude that although ozone exposure does not increase FSA in samples of airway and alveolar lining fluid, ozone exposure is associated with increased levels of TGFb2- a cytokine implicated in the pathogenesis of lung fibrosis.
For questions regarding this research project, including available data and progress status, contact: Research Division staff at (916) 445-0753
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