Ambient Particulate Matter Induces Interleukin8 Expression through an Alternative NF-κB (Nuclear Factor-Kappa B) Mechanism in Human Airway Epithelial Cells.

Autor:	Silbajoris, Robert¹, Osornio-Vargas, Alvaro R.², Simmons, Steven O.³, Reed, William⁴, Bromberg, Philip A.⁴, Dailey, Lisa A.¹, Samet, James M.¹ samet.james@epa.gov
Předmět:	Environmental exposure Particulate matter Analysis of variance Electrophysiology Epithelial cells Gene expression Interleukins Metabolism Metropolitan areas Polymerase chain reaction Research funding Respiratory mucosa Statistical hypothesis testing Statistics T-test (Statistics) Western immunoblotting Data analysis Reverse transcriptase polymerase chain reaction
Zdroj:	Environmental Health Perspectives. Oct2011, Vol. 119 Issue 10, p1379-1383. 5p.
Abstrakt:	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 (IL8) in human airway epithelial cells (HAECs) exposed to ambient PM collected in an urban area of Mexicali, Mexico. Methods: We studied IL8 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 IL8 mRNA expression relative to controls. PM exposure induced IL8 transcriptional activity in BEAS-2B cells that was dependent on the nuclear factor-kappa B (NF-κB) response element in the IL8 promoter. Chromatin immunoprecipitation (ChIP) assays showed a 3-fold increase in binding of the p65 (RelA) NF-κB isoform to the IL8 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. IL8 expression was blunted in a dose-dependent manner in BEAS-2B cells transduced with a lenti-virus encoding a dominant negative p65 mutant in which phosphorylation sites were inactivated. Conclusion: Taken together, these findings show that the increase in IL8 mRNA expression in HAECs exposed to PM10 (PM ≤ 10 µm in aerodynamic diameter) is mediated through an NF-κÈ-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. [ABSTRACT FROM AUTHOR]
Databáze:	GreenFILE
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