Science Inventory

Ambient particulate matter induces IL-8 expression through an alternative NF-kB mechanism in human airway epithelial cells

Citation:

SILBAJORIS, R. A., J. M. SAMET, L. A. DAILEY, S. SIMMONS, P. A. Bromberg, AND W. Reed. Ambient particulate matter induces IL-8 expression through an alternative NF-kB mechanism in human airway epithelial cells. ENVIRONMENTAL HEALTH PERSPECTIVES. National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, NC, 119(10):1379-83, (2011).

Impact/Purpose:

OBJECTIVE: To examine signaling events involved in the expression of the inflammatory gene interleukin-8 (lL-8) in human airway epithelial cells (HAEC) exposed to ambient PM collected in an urban area of Mexicali, Mexico.

Description:

BACKGROUND: Exposure to ambient air particulate matter (PM) has been shown to increase rates of cardio-pulmonary morbidity and mortality, but the underlying mechanisms are still not well understood. OBJECTIVE: To examine signaling events involved in the expression of the inflammatory gene interleukin-8 (lL-8) in human airway epithelial cells (HAEC) exposed to ambient PM collected in an urban area of Mexicali, Mexico. METHODS: IL-8 expression and regulatory signaling pathways were studied in cultured human airway epithelial cells exposed to 10-80 ug/cm² Mexicali PM suspended in media for 0-4 hr. RESULTS: Exposure resulted in a dose-dependent, 2-8-fold increase in IL-8 mRNA expression relative to controls. PM exposure induced IL-8 transcriptional activity in BEAS-2B cells that is dependent on the nuclearfactor kappa B(NF-kB) response element in the IL-8 promoter. Chromatin immunoprecipitation (ChIP) assays showed a 3-fold increase in binding of the p65 (Re1A)NF-kB isoform to the IL-8 promoter sequence in HAEC exposed to PM compared to controls. Western blot analyses showed elevated levels of phosphorylation of p65 but no changes in IkBα 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 the phosphorylation sites were inactivated. CONCLUSION: Taken together, these findings show that the increase in IL-8 mRNA expression in HAEC exposed to PM10 is mediated through an NF-kB-dependent signaling mechanism that occurs through a pathway involving direct phosphorylation of the transcription factor p65 in the absence of IkBα degradation. These data show that exposure to PM10 in ambient air can induce inflammatory responses by activating specific signaling mechanisms in human airway epithelial cells.

URLs/Downloads:

ENVIRONMENTAL HEALTH PERSPECTIVES   Exit

Record Details:

Record Type: DOCUMENT (JOURNAL/PEER REVIEWED JOURNAL)
Product Published Date: 10/01/2011
Record Last Revised: 10/04/2012
OMB Category: Other
Record ID: 233745