Diesel exhaust particles activate human bronchial epithelial cells to express inflammatory mediators in the airways: a review.
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.
Takizawa
H
H
The Department of Laboratory Medicine, Nippon Medical School, Tokyo, Japan. Takizawa-Phy@h.u-tokyo.ac.jp
Ohtoshi
T
T
Kawasaki
S
S
Abe
S
S
Sugawara
I
I
Nakahara
K
K
Matsushima
K
K
Kudoh
S
S
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*
D016207:Cytokines; D016209:Interleukin-8; D001335:Vehicle Emissions; D016178:Granulocyte-Macrophage Colony-Stimulating Factor