Diesel exhaust particles up-regulate expression of intercellular adhesion molecule-1 (ICAM-1) in human bronchial epithelial cells.
Epidemiological and experimental studies suggest that diesel exhaust particles (DEP) may play an active role in the increased respiratory mortality and morbidity. We have shown that DEP augmented the production of inflammatory cytokines by human airway epithelial cells in vitro. ICAM-1 has been shown to play an important role in the local accumulation of inflammatory cells. We studied the effect of DEP on ICAM-1 gene expression and surface expression in human bronchial epithelial cell line BEAS-2B. DEP (5-50 microg/ml) showed a stimulatory effect on ICAM-1 mRNA levels as evaluated by reverse transcription-polymerase chain reaction (RT-PCR). Flow cytometric analysis demonstrated an increased ICAM-1 expression on the epithelial cell surfaces. The soluble form of ICAM-1 molecules was also increased by the stimulation of DEP. In vitro neutrophil attachment onto DEP-stimulated epithelial cells was augmented, which was partially blocked by anti-ICAM-1 neutralizing antibody. Finally, these events were significantly inhibited by pretreatment with anti-oxidants pyrrolidine dithiocarbamate and N-acetyl cysteine, and p38 mitogen activated protein kinase (MAPK) inhibitor SB203580. These findings suggested that DEP induced up-regulation of ICAM-1 gene, and this process might be largely dependent on oxidant-mediated NF-kappaB activation and p38-MAPK pathways.
Takizawa
H
H
Department of Laboratory Medicine, University of Tokyo, School of Medicine, Hongo, Japan.
Abe
S
S
Ohtoshi
T
T
Kawasaki
S
S
Takami
K
K
Desaki
M
M
Sugawara
I
I
Hashimoto
S
S
Azuma
A
A
Nakahara
K
K
Kudoh
S
S
D001980:Bronchi / Q000166:cytology; D002448:Cell Adhesion; D002460:Cell Line; D005434:Flow Cytometry; D005742:Gasoline / Q000009:adverse effects*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics*; D009504:Neutrophils / Q000502:physiology; D020545:Respiratory Mucosa / Q000166:cytology; D012995:Solubility; D015854:Up-Regulation; D001335:Vehicle Emissions / Q000009:adverse effects*
D005742:Gasoline; D001335:Vehicle Emissions; D018799:Intercellular Adhesion Molecule-1