Ambient particulate matter induces interleukin-8 expression through an alternative NF-κB (nuclear factor-kappa B) mechanism in human airway epithelial cells

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Abstract

BACKGROUND: Exposure to ambient air particulate matter (PM) has been shown to increase rates of cardiopulmonary morbidity and mortality, but the underlying mechanisms are still not well understood.<br /><br />OBJECTIVE: We examined signaling events involved in the expression of the inflammatory gene interleukin-8 (IL-8) in human airway epithelial cells (HAECs) exposed to ambient PM collected in an urban area of Mexicali, Mexico.<br /><br />METHODS: We studied IL-8 expression and regulatory signaling pathways in cultured HAECs exposed to Mexicali PM suspended in media for 0-4 hr.<br /><br />RESULTS: Exposure resulted in a dose-dependent, 2- to 8-fold increase in IL-8 mRNA expression relative to controls. PM exposure induced IL-8 transcriptional activity in BEAS-2B cells that was dependent on the nuclear factor-kappa B (NF-κB) response element in the IL-8 promoter. Chromatin immunoprecipitation (ChIP) assays showed a 3-fold increase in binding of the p65 (RelA) NF-κB isoform to the IL-8 promoter sequence in HAECs exposed to PM. Western blot analyses showed elevated levels of phosphorylation of p65 but no changes in IκBα phosphorylation or degradation. IL-8 expression was blunted in a dose-dependent manner in BEAS-2B cells transduced with a lentivirus encoding a dominant negative p65 mutant in which phosphorylation sites were inactivated.<br /><br />CONCLUSION: Taken together, these findings show that the increase in IL-8 mRNA expression in HAECs exposed to PM10 (PM ≤ 10 μm in aerodynamic diameter) is mediated through an NF-κB-dependent signaling mechanism that occurs through a pathway involving direct phosphorylation of the transcription factor p65 in the absence of IκBα degradation. These data show that exposure to PM10 in ambient air can induce inflammatory responses by activating specific signaling mechanisms in HAECs.

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Silbajoris, R., Osornio-Vargas, A. R., Simmons, S. O., Reed, W., Bromberg, P. A., Dailey, L. A., & Samet, J. M. (2011). Ambient particulate matter induces interleukin-8 expression through an alternative NF-κB (nuclear factor-kappa B) mechanism in human airway epithelial cells. Environmental Health Perspectives, 119(10), 1379–1383. https://doi.org/10.1289/ehp.1103594

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