Diesel exhaust particles induce NF-kappa B activation in human bronchial epithelial cells in vitro: Importance in cytokine transcription

Fine particles derived from diesel engines (diesel exhaust particles, DEP) have attracted attention, since their density in industrial countries seems related to the increased prevalence of pulmonary diseases. Previous studie s have suggested that DEP have a potential to directly activate airway epit helial cells to produce and release inflammatory cytokines and mediators, a nd thus facilitate inflammatory responses in the lung, To elucidate the mol ecular mechanisms of their action, we studied here IL-8 gene expression, on e of the important cytokines in inflammatory responses, by Northern blot an alysis and run-on transcription assay. Suspended DEP (1-50 mu g/ml) increas ed the steady state levels of IL-8 mRNA, which was suggested to be largely due to increased transcriptional rates. Electrophoretic mobility shift assa y demonstrated that DEP induced increased binding to the specific moth of N F-kappa B, but not of transcription factor AP-1. The luciferase reporter ge ne assay using wild-type and mutated NF-kappa B-binding sequences showed th at DEP-induced NF-kappa B activation was involved in IL-8 transcription. Fi nally, both N-acetylcysteine and pyrrolidine dithiocarbamate attenuated the action of DEP on IL-8 mRNA expression, suggesting that oxidant-mediated pa thway might be involved in its processes. These results suggested that DEP activate NF-kappa B, which might be an important mechanism of its potential to increase the expression of inflammatory cytokines in vitro.