Ozone induces a proinflammatory response in primary human bronchial epithelial cells through mitogen-activated protein kinase activation without nuclear factor-κB activation.
Ground-level ozone (O3) is a ubiquitous environmental air pollutant that is a potent inducer of airway inflammation and has been linked with respiratory and cardiovascular morbidity and mortality. Some studies using transformed or immortalized cells have attributed O3-mediated expression of inflammatory cytokines with activation of the canonical NF-κB pathway. In this study, we sought to characterize the O3-mediated activation of cellular signaling pathways using primary human bronchial epithelial cells obtained from a panel of donors. We demonstrate that the O3-induced expression of proinflammatory cytokines requires the activation of the epidermal growth factor receptor/MEK/ERK and MKK4/p38 mitogen-activated signaling pathways but does not appear to involve activation of canonical NF-κB signaling. In addition to providing a novel mechanistic model for the O3-mediated induction of proinflammatory cytokines, these findings highlight the importance of using primary cells over cell lines in mechanistic studies.
1 Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, US Environmental Protection Agency, Chapel Hill, North Carolina.
Shaun D
SD
McCullough
Kelly E
KE
Duncan
Samantha M
SM
Swanton
Lisa A
LA
Dailey
David
D
Diaz-Sanchez
Robert B
RB
Devlin
D000393:Air Pollutants / Q000737:chemistry; D001980:Bronchi / Q000166:cytology* / Q000473:pathology; D002478:Cells, Cultured / Q000166:cytology; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000737:chemistry; D004847:Epithelial Cells / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007249:Inflammation; D020935:MAP Kinase Signaling System; D016328:NF-kappa B / Q000378:metabolism; D010126:Ozone / Q000737:chemistry*; D020545:Respiratory Mucosa / Q000166:cytology*; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000393:Air Pollutants; D004791:Enzyme Inhibitors; D016328:NF-kappa B; D010126:Ozone; D048051:p38 Mitogen-Activated Protein Kinases
airway; inflammation; kinase; ozone; pollution