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REPEATED EXPOSURES OF HUMAN RESPIRATORY EPITHELIAL CELLS TO OZONE SENSITIZES THE EFFECTS INDUCED BY SUBSEQUENT CHALLENGES TO AIR POLLUTANTS
Citation:
DOYLE, M., K. SEXTON, H. E. JEFFERIES, AND I. JASPERS. REPEATED EXPOSURES OF HUMAN RESPIRATORY EPITHELIAL CELLS TO OZONE SENSITIZES THE EFFECTS INDUCED BY SUBSEQUENT CHALLENGES TO AIR POLLUTANTS. Presented at Society of Toxicology Annual Meeting, San Diego, CA, March 05 - 09, 2006.
Description:
Toll-like receptor 3 (TLR3) plays an integral role in innate immunity through the recognition of and response to viral infections. Our previous findings have shown that exposure to diesel exhaust prior to viral infection causes an enhancement of TLR3 expression and signaling in respiratory epithelial cells, yet the mechanisms by which this occurs are not clear. Recent studies have demonstrated that type I interferons (IFN) can enhance the expression of TLR3. Since virus-induced IFN-¿ production was significantly enhanced by diesel exhaust, we investigated the role of IFN-¿ in the upregulation of TLR3 in respiratory epithelial cells. Treatment of A549 cells with 1 ng/ml of IFN-¿ significantly upregulated TLR3 mRNA levels as early as 2 hours after stimulation, whereas treatment with IFN-¿ had no significant effect on TLR3 mRNA levels. To determine whether IFN-ß upregulated TLR3 expression at the transcriptional level, we measured TLR3 promoter reporter activity. Treatment with IFN-¿ also resulted in a significant activation of the TLR3 promoter, which was dependent on the interferon-stimulated response element (ISRE) in the TLR3 promoter region. Taken together these observations provide evidence that IFN-ß is a strong inducer for the expression of TLR3 in respiratory epithelial cells.