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

Journal Article · Mon Feb 15 00:00:00 EST 2010 · Toxicology and Applied Pharmacology

DOI:https://doi.org/10.1016/j.taap.2009.11.011· OSTI ID:21344864

Tal, Tamara L ^[1]; Simmons, Steven O ^[2]; Silbajoris, Robert; Dailey, Lisa ^[3]; Cho, Seung-Hyun ^[4]; Ramabhadran, Ram ^[1]; Linak, William ^[4]; Reed, William; Bromberg, Philip A ^[5]

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1. Curriculum in Toxicology, University of North Carolina, Chapel Hill (United States)
2. Integrated Systems Toxicology, National Health and Environmental Effects Research Laboratory, U.S. EPA (United States)
3. Environmental and Public Health, National Health and Environmental Effects Research Laboratory, U.S. EPA (United States)
4. Air Pollution Prevention Control Division, National Risk Management Research Laboratory, U.S. EPA (United States)
5. Center for Environmental Medicine, Asthma, and Lung Biology, University of North Carolina, Chapel Hill (United States)

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.

• OSTI ID: 21344864
• Journal Information: Toxicology and Applied Pharmacology, Vol. 243, Issue 1; Other Information: DOI: 10.1016/j.taap.2009.11.011; PII: S0041-008X(09)00477-3; Copyright (c) 2009 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0041-008X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ADENOVIRUS
BIOPSY
DIESEL FUELS
EPITHELIUM
GENES
LUNGS
MEN
TOXICITY
TRANSCRIPTION
ANIMAL TISSUES
ANIMALS
BODY
DIAGNOSTIC TECHNIQUES
DISTILLATES
ENERGY SOURCES
FOSSIL FUELS
FUELS
GAS OILS
LIQUID FUELS
MALES
MAMMALS
MAN
MICROORGANISMS
ONCOGENIC VIRUSES
ORGANS
PARASITES
PETROLEUM
PETROLEUM DISTILLATES
PETROLEUM FRACTIONS
PETROLEUM PRODUCTS
PRIMATES
RESPIRATORY SYSTEM
VERTEBRATES
VIRUSES