Effects of ozone exposure on nuclear factor-kappaB activation and tumor necrosis factor-alpha expression in human nasal epithelial cells.
In this study we investigated a possible mechanism of the human airway inflammatory response to inhaled ozone (O(3)). Cultures of human nasal epithelial (HNE) cells, initiated from excised nasal turbinates and grown on collagen-coated Transwell tissue culture inserts, were exposed to 120, 240, or 500 ppb O(3) for 3 h. An electron spin resonance (ESR) signal that changed with time suggested free radical production in HNE cells exposed to O(3). Nuclear protein extracts were analyzed for the activated transcription factor NF-kappaB by electrophoretic mobility-shift assay (EMSA), and showed a small dose-response activation of NF-kappaB that coincided with O(3)-induced free radical production. Basal media were analyzed for the presence of tumor necrosis factor-alpha (TNF-alpha) using the enzyme-linked immunosorbent assay (ELISA). In cultures exposed to 120 ppb O(3), the mean TNF-alpha concentration was not significantly different from those exposed to air. However, exposure to 240 and 500 ppb O(3) significantly increased mean TNF-alpha expression, relative to controls, 16 h after exposure. These results support the hypothesis that the human airway epithelium plays a role in directing the inflammatory response to inhaled O(3) via free radical-mediated NF-kappaB activation.
Department of Environmental Health, University of Washington, Seattle, Washington, USA.
B G
BG
Nichols
J S
JS
Woods
D L
DL
Luchtel
J
J
Corral
J Q
JQ
Koenig
D000328:Adult; D000368:Aged; D004305:Dose-Response Relationship, Drug; D004578:Electron Spin Resonance Spectroscopy; D004591:Electrophoresis, Polyacrylamide Gel; D004926:Escherichia coli / Q000378:metabolism; D005260:Female; D005609:Free Radicals / Q000032:analysis; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000096:biosynthesis* / Q000235:genetics; D009297:Nasal Mucosa / Q000187:drug effects* / Q000378:metabolism; D010126:Ozone / Q000009:adverse effects*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*; D014420:Turbinates / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D005609:Free Radicals; D008070:Lipopolysaccharides; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D010126:Ozone