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Ozone Induces a Proinflammatory Response in Primary Human Bronchial Epithelial Cells Through Mitogen-Activated Protein Kinase Activation Without Nuclear Factor-kB Activation
Citation:
McCullough, S., K. Duncan, S. Swanton, L. Dailey, D. Diaz-Sanchez, AND R. Devlin. Ozone Induces a Proinflammatory Response in Primary Human Bronchial Epithelial Cells Through Mitogen-Activated Protein Kinase Activation Without Nuclear Factor-kB Activation. AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY. American Thoracic Society, New York, NY, 51(3):426-35, (2014).
Impact/Purpose:
As the barrier between the lung and the environment, respiratory epithelial cells play an important role as modulators of the pro-inflammatory response to environmental pollutant exposure6,7. The expression of pro-inflammatory cytokines by these cells, such as IL-8, IL-6, IL-1α, and IL-1β, is associated with the induction of airway inflammation in humans following O3 exposure. However, the mechanisms underlying the induction of these genes have not been thoroughly studied. In this study we characterized the upstream signaling pathways responsible for the induction of O3-induced expression of pro-inflammatory cytokines in phBEC. Here we report the use of a phBEC ALI culture model to examine the role of MAP kinase activation in the O3-mediated induction of pro-inflammatory cytokines in vitro.
Description:
Ground-level ozone (O3) is a ubiquitous environmental air pollutant that is a potent inducer of airway inflammation and has been linked with both 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 pro-inflammatory 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 pro-inflammatory cytokines, these findings highlight the importance of using primary cells over cell lines in mechanistic studies.