当前位置： SCI文献检索 > TOXICOLOGY AND APPLIED PHARMACOLOGY期刊下所有文献 > Differential transcriptional regulation of IL-8 expression by human airway epithelial cells exposed to diesel exhaust particles.

Differential transcriptional regulation of IL-8 expression by human airway epithelial cells exposed to diesel exhaust particles.

Abstract：

:Exposure to diesel exhaust particles (DEP) induces inflammatory signaling characterized by MAP kinase-mediated activation of NFkB and AP-1 in vitro and in bronchial biopsies obtained from human subjects exposed to DEP. NFkB and AP-1 activation results in the upregulation of genes involved in promoting inflammation in airway epithelial cells, a principal target of inhaled DEP. IL-8 is a proinflammatory chemokine expressed by the airway epithelium in response to environmental pollutants. The mechanism by which DEP exposure induces IL-8 expression is not well understood. In the current study, we sought to determine whether DEP with varying organic content induces IL-8 expression in lung epithelial cells, as well as, to develop a method to rapidly evaluate the upstream mechanism(s) by which DEP induces IL-8 expression. Exposure to DEP with varying organic content differentially induced IL-8 expression and IL-8 promoter activity human airway epithelial cells. Mutational analysis of the IL-8 promoter was also performed using recombinant human cell lines expressing reporters linked to the mutated promoters. Treatment with a low organic-containing DEP stimulated IL-8 expression by a mechanism that is predominantly NFkB-dependent. In contrast, exposure to high organic-containing DEP induced IL-8 expression independently of NFkB through a mechanism that requires AP-1 activity. Our study reveals that exposure to DEP of varying organic content induces proinflammatory gene expression through multiple specific mechanisms in human airway epithelial cells. The approaches used in the present study demonstrate the utility of a promoter-reporter assay ensemble for identifying transcriptional pathways activated by pollutant exposure.

journal_name

Toxicol Appl Pharmacol

journal_title

Toxicology and applied pharmacology

authors

Tal TL,Simmons SO,Silbajoris R,Dailey L,Cho SH,Ramabhadran R,Linak W,Reed W,Bromberg PA,Samet JM

doi

10.1016/j.taap.2009.11.011

subject

Has Abstract

pub_date

2010-02-15 00:00:00

pages

46-54

issue

eissn

0041-008X

issn

1096-0333

pii

S0041-008X(09)00477-3

journal_volume

243

pub_type

杂志文章

在线工具

Differential transcriptional regulation of IL-8 expression by human airway epithelial cells exposed to diesel exhaust particles.