title: Diesel exhaust particles activate human bronchial epithelial cells to express inflammatory mediators in the airways: a review.
abstract: 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.
  
  
  METHODS
  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)-kappaB, 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-kappaB binding motifs indicated that the activation of NF-kappaB was essential for IL-8 gene upregulation by reporter gene assay.
  
  
  CONCLUSIONS
  These results suggested that DEP activate NF-kappaB, which might be an important pathway for the expression of inflammatory cytokines in vitro.
authors.affiliation: The Department of Laboratory Medicine, Nippon Medical School, Tokyo, Japan. Takizawa-Phy@h.u-tokyo.ac.jp
authors.forename: H
authors.initials: H
authors.lastname: Takizawa
authors.forename: T
authors.initials: T
authors.lastname: Ohtoshi
authors.forename: S
authors.initials: S
authors.lastname: Kawasaki
authors.forename: S
authors.initials: S
authors.lastname: Abe
authors.forename: I
authors.initials: I
authors.lastname: Sugawara
authors.forename: K
authors.initials: K
authors.lastname: Nakahara
authors.forename: K
authors.initials: K
authors.lastname: Matsushima
authors.forename: S
authors.initials: S
authors.lastname: Kudoh
mesh_terms: D001980:Bronchi / Q000276:immunology*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D004847:Epithelial Cells / Q000276:immunology*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis*; D006801:Humans; D066298:In Vitro Techniques; D007249:Inflammation / Q000276:immunology*; D016209:Interleukin-8 / Q000096:biosynthesis*; D012130:Respiratory Hypersensitivity / Q000276:immunology*; D001335:Vehicle Emissions / Q000009:adverse effects*
chemical_list: D016207:Cytokines; D016209:Interleukin-8; D001335:Vehicle Emissions; D016178:Granulocyte-Macrophage Colony-Stimulating Factor