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Am. J. Respir. Cell Mol. Biol., Volume 22, Number 3, March, 2000 296-303

Diesel Exhaust (DE)-Induced Cytokine Expression in Human Bronchial Epithelial Cells
A Study with a New Cell Exposure System to Freshly Generated DE In Vitro

Shinji Abe, Hajime Takizawa, Isamu Sugawara, and Shoji Kudoh

Fourth Department of Internal Medicine, Nippon Medical School; Department of Laboratory Medicine, University of Tokyo, School of Medicine; and Department of Molecular Pathology, The Research Institute of Tuberculosis, Tokyo, Japan

We devised a new in vitro cell exposure system to freshly generated diesel exhaust (DE), different from conventional in vitro culture systems, to examine the effects of DE on human epithelial cells. Using this system, we investigated the effects of DE on cytokine gene expressions in BET-1A human bronchial epithelial cells. DE significantly decreased [3H]thymidine incorporation into BET-1A cells. DE had a significant stimulatory effect on interleukin (IL)-8 release to a marked degree. IL-8 and transforming growth factor (TGF)-beta 1 messenger RNA (mRNA) expression were induced by DE in a time-dependent manner. The gas obtained by filtration of DE alone did not show a sustained increase in IL-8 protein levels and showed no induction of IL-8 mRNA, suggesting that DE particles (DEPs) play an important role in the induction of IL-8 at both mRNA and protein levels. Antioxidants, pyrrolidine dithiocarbamate, and N-acetyl-L-cysteine significantly inhibited IL-8 mRNA and protein levels by BET-1A cells. These results indicate that freshly generated DEPs may be important in the induction of cytokines such as IL-8 and TGF-beta 1 relevant to allergic airway inflammation.




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