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

摘要

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.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. METHODS: We studied IL-8 expression and regulatory signaling pathways in cultured HAECs exposed to Mexicali PM suspended in media for 0-4 hr. 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-kappaB) response element in the IL-8 promoter. Chromatin immunoprecipitation (ChIP) assays showed a 3-fold increase in binding of the p65 (RelA) NF-kappaB 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 IkappaBalpha 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. CONCLUSION: Taken together, these findings show that the increase in IL-8 mRNA expression in HAECs exposed to PM10 (PM