Autor: |
Takizawa, Hajime, Ohtoshi, Takayuki, Kawasaki, Shin, Abe, Shinji, Sugawara, Isamu, Nakahara, Kazuhiko, Matsushima, Kouji, Kudoh, Shoji |
Předmět: |
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Zdroj: |
Respirology; Jun2000, Vol. 5 Issue 2, p197-203, 7p |
Abstrakt: |
Objective:Epidemiological as well as experimental studies suggest that particulate air pollutants, including diesel exhaust particles (DEP), may play a role in the recent increase of respiratory morbidity and mortality. We studied the effect of DEP on the production of inflammatory cytokines and mediators including IL-8 and granulocyte macrophage colony stimulating factor (GM-CSF) by human airway epithelial cells in vitro. Methodology:Suspended DEP were added to cultured normal human bronchial epithelial cells or transformed BEAS-2B cells. The release of cytokines and mediators was evaluated by enzyme-linked immunosorbent assay. The transcriptional levels of IL-8 mRNA was studied by northern blot analysis and run-on transcription assay. Activation of transcription factors was assessed by electrophoretic mobility shift assay. Results: Non-toxic doses of suspended DEP showed a significant stimulatory effect on IL-8 and GM-CSF production by airway epithelial cells. Diesel exhaust particles increased the steady-state levels of IL-8 mRNA, which was suggested to be largely due to increased transcriptional rates. Electrophoretic mobility shift assay demonstrated that DEP induced increased binding to the specific motif of nuclear factor (NF)-κB, but not of transcription factor AP-1. Both N-acetylcysteine and pyrrolidine dithiocarbamate attenuated the action of DEP on IL-8 mRNA expression, suggesting that oxidant-mediated pathway might be involved in its processes. Transient transfection of airway epithelial cells with wild and NF-κB binding motifs indicated that the activation of NF-κB was essential for IL-8 gene upregulation by reporter gene assay. Conclusions: These results suggested that DEP activate NF-κB, which might be an important pathway for the expression of inflammatory cytokines in vitro. [ABSTRACT FROM AUTHOR] |
Databáze: |
Complementary Index |
Externí odkaz: |
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