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Diesel exhaust particles activate human bronchial epithelial cells to express inflammatory mediators in the airways: A review
Author(s) -
Takizawa Hajime,
Ohtoshi Takayuki,
Kawasaki Shin,
Abe Shinji,
Sugawara Isamu,
Nakahara Kazuhiko,
Matsushima Kouji,
Kudoh Shoji
Publication year - 2000
Publication title -
respirology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 85
eISSN - 1440-1843
pISSN - 1323-7799
DOI - 10.1046/j.1440-1843.2000.00245.x
Subject(s) - pyrrolidine dithiocarbamate , electrophoretic mobility shift assay , microbiology and biotechnology , transcription factor , transfection , messenger rna , interleukin 8 , in vitro , respiratory epithelium , chemokine , immunology , cytokine , biology , medicine , inflammation , nf κb , respiratory system , gene , biochemistry
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 .