Ozone Induces a Proinflammatory Response in Primary Human Bronchial Epithelial Cells through Mitogen-Activated Protein Kinase Activation Without Nuclear Factor-κB Activation
Ozone Induces a Proinflammatory Response in Primary Human Bronchial Epithelial Cells through Mitogen-Activated Protein Kinase Activation Without Nuclear Factor-κB Activation
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DOI：
10.1165/rcmb.2013-0515oc
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发表时间：
2014-09-01
影响因子：
6.4
通讯作者：
Devlin, Robert B.
中科院分区：
文献类型：
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作者：
McCullough, Shaun D.;Duncan, Kelly E.;Devlin, Robert B.
地面臭氧（O-3）是一种普遍存在的环境空气污染物，是气道炎症的有效诱导剂，与呼吸道和心血管疾病的发病率和死亡率有关。一些使用转化或永生化细胞的研究将O-3介导的炎性细胞因子表达归因于经典NF-κ B途径的激活。在这项研究中，我们试图用从一组供体中获得的原代人支气管上皮细胞来表征O-3介导的细胞信号通路的激活。我们证明，O-3诱导的促炎细胞因子的表达需要表皮生长因子受体/MEK/ERK和MKK 4/p38丝裂原激活的信号通路的激活，但似乎不涉及典型的NF-κ B信号的激活。除了提供一个新的机制模型的O-3介导的诱导促炎细胞因子，这些研究结果突出了使用原代细胞在机制研究中的细胞系的重要性。
Ground-level ozone (O-3) 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 O-3-mediated expression of inflammatory cytokines with activation of the canonical NF-kappa B pathway. In this study, we sought to characterize the O-3-mediated activation of cellular signaling pathways using primary human bronchial epithelial cells obtained from a panel of donors. We demonstrate that the O-3-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-kappa B signaling. In addition to providing a novel mechanistic model for the O-3-mediated induction of proinflammatory cytokines, these findings highlight the importance of using primary cells over cell lines in mechanistic studies.