OZONE-INDUCED ENHANCEMENT OF THE MESSENGE R-RNA EXPRESSION OF CHEMOKINES AND REDUCTION OF THE MESSENGER-RNA EXPRESSION OF TISSUE INHIBITORSOF MATRIX METALLOPROTEINASES IN THE HUMAN BRONCHIAL EPITHELIAL-CELL LINE BEAS-2B

The inhalation of ozone induces an inflammatory reaction and morpholog ic damage of lung tissue. Whereas early changes are reversible repeate d ozone effects may give rise to lasting alterations and could favor t he development of chronic lung disease. The question was raised whethe r ozone altered the gene expression of chemokines, matrix metalloprote inases and tissue inhibitors of matrix metalloproteinases by bronchiai epithelial cells. Cells of the human bronchial epithelial cell line B EAS-2B were exposed to 200, 600 and 2000 mu g/m(3) ozone for one hour. At several time points during the following 24 hours the mRNA of the chemokines IL-8. Gr alpha, Gro beta, Gro gamma and MCP-1, of the matri x metalloproteinases MMP-1 and MMP-9, and of their inhibitors TIMP-1 a nd TIMP-2 were determined by reverse transcription and semiquantitativ e polymerase chain reaction. Ozone caused a dose-dependent increase of the mRNA of all five chemokines. It reduced the mRNA of TIMP-1 and TI MP-2, but it had no effect on the matrix metalloproteinases. Since the secretion of all studied products is transcriptionally regulated, the alterations of the mRNA levels should be reflected by corresponding s ecretory rates. Increased release of cytokines is expected to contribu te to the observed ozone-induced inflammatory changes. Reduced release of metalloproteinase inhibitors may allow increased tissue destructio n by matrix metalloproteinases.