Ozone Induces a Proinflammatory Response in Primary Human Bronchial Epithelial Cells through Mitogen-Activated Protein Kinase Activation Without Nuclear Factor-κB Activation

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.

Assessment of biological responses of EpiAirway 3-D cell constructs versus A549 cells for determining toxicity of ambient air pollution

“…This is in contrast to other studies which have shown O 3 -induced cytokine responses in differentiated NHBE cells at O 3 concentrations comparable to what was used in this study (Ahmad et al, 2011, Damera et al, 2009, McCullough et al, 2014). It is important to note that in these other studies the amount of time the NHBE cells were maintained at ALI conditions to differentiate prior to exposure varied from a couple of days to 2 weeks.…”

Antibacterial Defense of Human Airway Epithelial Cells from Chronic Obstructive Pulmonary Disease Patients Induced by Acute Exposure to Nontypeable Haemophilus influenzae: Modulation by Cigarette Smoke

“…Based on our findings, it can be speculated that MAPK signaling has a more prominent role in CS-induced airway epithelial inflammatory responses than NF-κB. This is further supported by findings from a recent study examining ozone-induced proinflammatory responses by differentiated airway epithelial cells, revealing the MAPKdependent and NF-κB-independent induction of inflammatory mediators [53] .…”

Developing and Emerging Clinical Asthma Phenotypes

“…Pollutants, such as ozone, 74 nitrogen oxide, 75 and particular matter <2.5 mm in diameter, 76 can induce airway hyperresponsiveness and neutrophilic airway inflammation; however, the mechanism is unknown. Probable air pollutants cause oxidative injury to the airways, which leads to inflammation, remodeling, and increased risk of sensitization.…”