Abstract:
: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.
journal_name
Am J Respir Cell Mol Biolauthors
McCullough SD,Duncan KE,Swanton SM,Dailey LA,Diaz-Sanchez D,Devlin RBdoi
10.1165/rcmb.2013-0515OCsubject
Has Abstractpub_date
2014-09-01 00:00:00pages
426-35issue
3eissn
1044-1549issn
1535-4989journal_volume
51pub_type
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