Diesel exhaust particles activate human bronchial epithelial cells to express inflammatory mediators in the airways: a review.

Abstract

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. 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. 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. These results suggested that DEP activate NF-kappaB, which might be an important pathway for the expression of inflammatory cytokines in vitro.