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Lymphocyte Gene Expression Characteristic of Immediate Airway Responses (IAR) and Methacholine (MCH) Hyperresponsiveness in Mice Sensitized and Challenged with Isocyanates
Citation:
SELGRADE, M. K., C. M. PUCHEU-HASTON, E. BOYKIN, AND S. D. HESTER. Lymphocyte Gene Expression Characteristic of Immediate Airway Responses (IAR) and Methacholine (MCH) Hyperresponsiveness in Mice Sensitized and Challenged with Isocyanates. Presented at Amnual Society of Toxicology, Baltimore, MD, March 15 - 19, 2009.
Impact/Purpose:
Exposure to isocyanates has been associated with occupational airway diseases, including asthma. Previously we reported on respiratory and immune responses following dermal sensitization and intranasal challenge of BALB/c mice with 6 different isocyanates.
Description:
Exposure to isocyanates has been associated with occupational airway diseases, including asthma. Previously we reported on respiratory and immune responses following dermal sensitization and intranasal challenge of BALB/c mice with 6 different isocyanates. The purpose of this study was to determine whether differences in gene expression in the draining lymph node could be related to phenotypic differences that were observed in responses to the different isocyanates. RNA was extracted from lymph nodes of mice exposed to 2% dicyclohexylmethane-4,4’diisocyanate (HMDI), 1% toluene diisocyanate (TDI), and 1% meta-tetramethylene xylene isocyanate (TMXDI) following the intranasal challenge. IAR were observed in mice treated with TDI and HMDI, but not TMXDI. Increased MCH hyperresponsiveness was observed in mice treated with HMDI and TMXDI, but not TDI. Affymetrix chips were used to analyze treatment-associated changes in gene expression RNA. A statistical filter was used to assess difference from vehicle control (p<0.05) corrected for multiple observations. A Venn diagram was generated showing changes in expression of 2475 genes in common with HMDI and TDI, hence possibly associated with the IAR, and in expression of 88 genes in common with HMDI and TMXDI, hence possibly associated with the MCH response. Amongst the 2475 genes pathway analysis revealed a number of genes associated with the T-cell receptor and T-cell activation. In contrast, amongst the 88 genes, pathway analysis identified genes associated with cell cycle and tight junctions, but T-cell activation genes were notably absent. These genes (and/or pathways) could potentially be used to predict airway responses to other isocyanates and possibly other low molecular weight chemicals. This abstract does not reflect EPA policy.