Activation of Transcription Factors by Diesel Exhaust Particles in Human Bronchial Epithelial Cells in Vitro.

Diesel exhaust particles (DEP) are suspected to be involved in the aggravation of inflammatory respiratory diseases. Wehave shown previously, in human bronchial epithelial cell line 16HBE 14o-, that DEP induced the release of the proinflammatory cytokines granulocytemacrophage colony-stimulating factor (GM-CSF) and interleukin-8 (IL-8) after 24 h of exposure. Gene expression of these cytokines is regulated by transcription factors including NF-kappaB and AP-1, which are known to be sensitive to oxidative stress. Their activation by DEP was investigated in comparison with a pure oxidant, H2O2. A 4-h exposure to DEP (10 mug/cm2) or to H2O2 (100 muM) increased NF-kappaB DNA binding in 16HBE cells as assessed by electrophoretic mobility shift assay.AP-1 was only activated by H2O2 in the same conditions. Organic extracts of DEP increased NF-kappaB DNA binding as did native DEP,suggesting the role of the polycyclic aromatic hydrocarbons (PAH) in this NF-kappaB increased DNA binding. Dimethylthiourea (DMTU), an ...