ToxSci Advance Access published online on September 1, 2005
Toxicological Sciences, doi:10.1093/toxsci/kfi311
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1 Department of Biochemistry and Molecular Biology, Medical School Duluth, University of Minnesota, Duluth, Minnesota 55812
* To whom correspondence should be addressed. Both trimellitic anhydride (TMA), a small molecular weight chemical, and ovalbumin (OVA), a reference protein allergen, cause asthma with eosinophilia. To test the hypothesis that different allergens elicit symptoms of asthma via different effector pathways, gene expression was compared in lungs of Balb/c mice sensitized with either TMA or OVA, followed by intratracheal challenge with TMA conjugated to mouse serum albumin (TMA-MSA) or OVA, respectively. Sensitized animals challenged with mouse serum albumin (MSA) alone were controls. Seventy-two hours after challenge, lung eosinophil peroxidase indicated that both allergens caused the same significant change in eosinophilia. Total RNA was isolated from lung lobes of 6-8 animals in each of 4 treatment groups and hybridized to Affymetrix U74Av2 GeneChips. False discovery rates (q-values) were calculated from an overall F test to identify candidate genes with differences in expression for the 4 groups. Using a q-value cutoff of 0.1, 853 probe sets had significantly different expression across the 4 treatment groups. Of these 853 probe sets, 376 genes had an Experimental/Control ratio of greater than 1.2 or less than 1/1.2 for either OVA- or TMA-treated animals, and 249 of the 376 genes were uniquely up- or down-regulated for OVA or TMA (i.e. differentially expressed with the allergen). qRT-PCR analysis of selected transcripts confirmed the gene expression analysis. Increases in both arginase transcript and enzyme activity were significantly greater in OVA-induced asthma compared to TMA-induced asthma. These data suggest that pathways of arginine metabolism and the importance of nitric oxide may differ in OVA- and TMA-induced asthma.
Received June 28, 2005
Accepted August 30, 2005
Immunotoxiocology
Arginase Activity Differs with Allergen in the Effector Phase of Ovalbumin- vs Trimellitic Anhydride-Induced Asthma
2 Department of Veterinary and Biomedical Science, College of Veterinary Medicine, University of Minnesota, St. Paul, Minnesota 55108
3 Department of Mathematics and Statistics, College of Science and Engineering, University of Minnesota, Duluth, Minnesota 55812
4 Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, California 95616
Jean F. Regal, E-mail: jregal{at}d.umn.edu
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