Abstract |
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 four 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 four groups. Using a q-value cutoff of 0.1, 853 probe sets had significantly different expression across the four 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.
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Authors | Amy L Greene, Mark S Rutherford, Ronald R Regal, Gail H Flickinger, Julie A Hendrickson, Cecilia Giulivi, Margaret E Mohrman, Daniel G Fraser, Jean F Regal |
Journal | Toxicological sciences : an official journal of the Society of Toxicology
(Toxicol Sci)
Vol. 88
Issue 2
Pg. 420-33
(Dec 2005)
ISSN: 1096-6080 [Print] United States |
PMID | 16141432
(Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)
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Chemical References |
- Allergens
- Phthalic Anhydrides
- RNA, Messenger
- trimellitic anhydride
- Ovalbumin
- Peroxidase
- Arginase
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Topics |
- Allergens
(administration & dosage, pharmacology)
- Animals
- Arginase
(genetics, metabolism)
- Asthma
(chemically induced, enzymology, immunology)
- Disease Models, Animal
- Eosinophilia
(chemically induced, enzymology, immunology)
- Eosinophils
(drug effects, enzymology, immunology)
- Female
- Gene Expression
(drug effects)
- Intubation, Intratracheal
- Mice
- Mice, Inbred BALB C
- Microchip Analytical Procedures
- Ovalbumin
(administration & dosage, pharmacology)
- Peroxidase
(metabolism)
- Phthalic Anhydrides
(administration & dosage, pharmacology)
- RNA, Messenger
(metabolism)
- Reverse Transcriptase Polymerase Chain Reaction
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