You are here:
DIESEL EXHAUST PARTICLE INDUCED GENE EXPRESSION CHANGES IN A MURINE MUCOSAL SENSITIZATION MODEL
Citation:
STEVENS, T., M. J. DANIELS, W. P. LINAK, AND M. I. GILMOUR. DIESEL EXHAUST PARTICLE INDUCED GENE EXPRESSION CHANGES IN A MURINE MUCOSAL SENSITIZATION MODEL. Presented at American Thoracic Society Annual Meeting, San Francisco, CA, May 18 - 23, 2007.
Description:
Studies in humans and animals have shown diesel exhaust particles (DEP) can act as an immunological adjuvant to enhance the development of allergic lung disease and this effect is influenced by the chemical composition of the DEP. The adjuvancy of NIST SRM 2975 (NDEP) generated from a heavy forklift, DEP generated from a diesel engine used to power a compressor (CDEP), and an automobile generated DEP (ADEP), were assessed in a murine ovalbumin mucosal sensitization model. These samples differed in the percentage of extractable organic material; NDEP, CDEP, and ADEP contained 1.5%, 18.9%, and 67%, respectively. Immune and inflammatory endpoints in the lung showed that CDEP > ADEP > NDEP > saline with respect to adjuvancy as measured by eosinophilic inflammation, TH2 cytokines, and serum IgG1 antibodies. To understand early signaling events that influenced the various degrees of adjuvancy, BALB/c mice were instilled intranasally with saline or 150 ug of NDEP, ADEP, or CDEP with or without 20 ug of ovalbumin (ova) on days 0 and 13 and necropsied 18 hrs later. Lung RNA was isolated, labeled, and hybridized to Affymetrix Mouse 430A GeneChips. Gene expression was normalized using Robust Multichip Average Analysis (RMA). All DEP/ova exposures resulted in differential gene expression changes in the cytokine-cytokine receptor interaction pathway, including chemokines CCL2, 3, 5, 7, 8, 11, 12, and 22. The most robust gene expression changes were in the CDEP/ova exposed mice, which also included altered pathways involved in antigen processing and presentation, cell adhesion, natural killer cell-mediated cytotoxicity, and toll-like receptor signaling. Future studies will identify which chemical components of the DEPs are involved in the modulation of these pathways. (Supported by the EPA Training Agreement CT 829472. This abstract does not reflect EPA policy.)