Effect of ozone and nitrogen dioxide on the release of proinflammatory mediators from bronchial epithelial cells of nonatopic nonasthmatic subjects and atopic asthmatic patients in vitro.
BACKGROUND
Although studies have suggested that ozone (O3) and nitrogen dioxide (NO2) may play a role in the pathogenesis of asthma, the underlying mechanisms are not clear.


OBJECTIVE
We aimed to investigate the effects of O3 and NO2 on the release of IL-8, GM-CSF, RANTES, and soluble intercellular adhesion molecule 1 (sICAM-1) from human bronchial epithelial cells (HBECs) of nonatopic nonasthmatic subjects (nonasthmatic subjects) and atopic subjects with mild asthma (asthmatic subjects) in vitro.


METHODS
We cultured HBECs from bronchial biopsy specimens of nonasthmatic and asthmatic subjects; exposed these for 6 hours to air, 10 to 100 ppb O3, or 100 to 400 ppb NO2; and analyzed the release of IL-8, GM-CSF, RANTES, and sICAM-1 after 24 hours' incubation.


RESULTS
There was no significant difference between the constitutive release of IL-8, GM-CSF, and sICAM-1 from HBECs of asthmatic and nonasthmatic subjects. RANTES was detected only in HBECs derived from asthmatic subjects. Exposure of HBECs of asthmatic subjects to both 50 to 100 ppb O3 and 200 to 400 ppb NO2 significantly increased the release of IL-8, GM-CSF, RANTES, and sICAM-1 from these cells after 24 hours of incubation. However, 50 to 100 ppb O3 and 200 to 400 ppb NO2 led to a significant increase in release of only IL-8 and sICAM-1 from HBECs of nonasthmatic subjects after 24 hours' incubation. A comparison between the pollutant-induced release of mediators demonstrated that 100 ppb O3-induced release of GM-CSF and sICAM-1 was significantly greater in HBECs of asthmatic subjects (medians, 0.59 and 27.4 pg/microg cellular protein, respectively) than in HBECs of nonasthmatic subjects (medians, 0.27 and 14.4 pg/microg cellular protein, respectively; P < .02).


CONCLUSIONS
These results suggest that O3 and NO2 may modulate airway diseases, such as asthma, by increasing the release of inflammatory mediators from bronchial epithelial cells and that the cells of asthmatic subjects may be more susceptible to the adverse effects of these pollutants.
Bayram
H
H
Department of Respiratory Medicine, School of Medicine, University of Dicle, Diyarbakir, Turkey.
Sapsford
R J
RJ
Abdelaziz
M M
MM
Khair
O A
OA
D001249:Asthma / Q000473:pathology*; D001980:Bronchi / Q000166:cytology*; D002478:Cells, Cultured; D018946:Chemokine CCL5 / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000473:pathology*; D018836:Inflammation Mediators / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D009585:Nitrogen Dioxide / Q000494:pharmacology*; D010126:Ozone / Q000494:pharmacology*; D012636:Secretory Rate / Q000187:drug effects
D018946:Chemokine CCL5; D018836:Inflammation Mediators; D016209:Interleukin-8; D018799:Intercellular Adhesion Molecule-1; D010126:Ozone; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D009585:Nitrogen Dioxide