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Increased Transcription of Immune and Metabolic Pathways in Naive and Allergic Mice Exposed to Diesel Exhaust
Citation:
STEVENS, T., Q. T. KRANTZ, W. P. LINAK, S. D. HESTER, AND M I. GILMOUR. Increased Transcription of Immune and Metabolic Pathways in Naive and Allergic Mice Exposed to Diesel Exhaust. TOXICOLOGICAL SCIENCES. Society of Toxicology, RESTON, VA, 102(2):359-370, (2008).
Impact/Purpose:
Diesel exhaust (DE) has been shown to enhance allergic sensitization in animals following high dose and/or chronic exposure scenarios. The purpose of this study was to determine if short term exposures to diluted DE enhance allergic immune responses to antigen, and identify possible mechanisms using microarray technology. This study shows for the first time early changes in gene expression induced by the combination of diesel inhalation and antigen sensitization, which resulted in stronger development of an allergic asthma phenotype. This could be used as further evidence linking air pollution in general and diesel in particular to the rise in asthma and possibly used in determining air quality standards.
Description:
Diesel exhaust (DE) has been shown to enhance allergic sensitization in animals following high dose instillation or chronic inhalation exposure scenarios. The purpose of this study was to determine if short term exposures to diluted DE enhance allergic immune responses to antigen, and identify possible mechanisms using microarray technology. BALB/c mice were exposed to filtered air or diluted DE to yield particle concentrations of 500 or 2000 μg/m3 4 hr/day on days 0-4. Mice were sensitized intranasally with ovalbumin (OVA) antigen or saline on days 0-2, and 18 and all were challenged with OVA on day 28. Mice were necropsied either 4 hrs after the last DE exposure on day 4, or 18, 48, and 96 hrs after challenge. Immunological endpoints included OVA-specific serum IgE, biochemical and cellular profiles of bronchoalveolar lavage (BAL), and cytokine production in the BAL. OVA-sensitized mice exposed to both concentrations of DE had increased eosinophils, neutrophils, lymphocytes, and IL-6 post-challenge compared to OVA control, while DE/saline exposure yielded increases in neutrophils at the high dose only. Microarray analysis demonstrated distinct gene expression profiles for the high dose DE/OVA and DE/saline groups. DE/OVA induced pathways involved in oxidative stress and metabolism while DE in the absence of allergen sensitization modulated cell cycle control, growth and differentiation, G-proteins, and cell adhesion pathways. This study shows for the first time early changes in gene expression induced by the combination of diesel exhaust inhalation and antigen sensitization, which resulted in stronger development of an allergic asthma phenotype.
