Induction of the epidermal growth factor receptor and its ligands in nasal epithelium by ozone.
BACKGROUND
Ozone is a photochemical oxidant pollutant that is an important public health hazard. Although the inflammatory response that occurs in response to ozone inhalation is well characterized, the mechanisms underlying epithelial cell activation are not well understood.


OBJECTIVE
Because the epidermal growth factor receptor (EGFR) is a central regulator of epithelial function, we tested the hypothesis that nasal epithelial cells respond to ozone-induced oxidant stress by modulating expression of the EGFR and its ligands, EGF and transforming growth factor-alpha (TGF-alpha).


METHODS
Normal volunteers were exposed to air or 400 parts per billion ozone for 2 hours, and then nasal biopsy specimens were harvested 6 hours later for immunohistochemical analysis of EGFR, EGF, and TGF-alpha. Nasal epithelial cell cultures were exposed in vitro to ozone or TNF-alpha; mediator release was measured by ELISA and cellular EGFR expression by immunoblotting and fluorescence-activated cell sorting analysis.


RESULTS
Epithelial expression of the EGFR, EGF, and TGF-alpha were all significantly (P <.05) increased in the nasal biopsy specimens after ozone exposure, and there was a significant positive correlation between EGFR expression and the increase in neutrophil numbers in the nasal epithelium (P =.001, rho = 0.87). In vitro exposure of primary nasal epithelial cell cultures to ozone had no effect on EGFR expression, even though IL-8 release was enhanced. In contrast, exposure to TNF-alpha caused EGFR levels to increase significantly.


CONCLUSIONS
These data suggest that the ozone-induced increase in EGFR expression observed in vivo is indirect, perhaps mediated by neutrophil-derived TNF-alpha.
Polosa
Riccardo
R
Respiratory Cell and Moleculat Biology Division, School of Medicine, Southampton General Hospital, Southampton, United Kingdom.
Sapsford
Raymond J
RJ
Dokic
Dejan
D
Cacciola
Rossella R
RR
Prosperini
Gaetano
G
Devalia
Jagdish L
JL
Holgate
Stephen T
ST
Howarth
Peter H
PH
Davies
Donna E
DE
D000328:Adult; D004797:Enzyme-Linked Immunosorbent Assay; D004815:Epidermal Growth Factor / Q000378:metabolism*; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008024:Ligands; D008297:Male; D008875:Middle Aged; D009297:Nasal Mucosa / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D009504:Neutrophils / Q000166:cytology; D010083:Oxidants, Photochemical / Q000494:pharmacology*; D010126:Ozone / Q000494:pharmacology*; D016211:Transforming Growth Factor alpha / Q000378:metabolism
D008024:Ligands; D010083:Oxidants, Photochemical; D016211:Transforming Growth Factor alpha; D004815:Epidermal Growth Factor; D010126:Ozone; D066246:ErbB Receptors