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Murine Model of Allergen Induced Asthma
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Dissection of experimental asthma with DNA microarray analysis identifies arginase in asthma pathogenesis
Nives Zimmermann1, Nina E King, Johanne Laporte
1Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45229, USA.
The Journal of Clinical Investigation
|June 19, 2003
Summary
Investigating experimental asthma in mice revealed altered gene expression, particularly in arginine metabolism pathways involving arginase I and II. This highlights potential new therapeutic targets for allergic airway diseases.
Area of Science:
- Immunology
- Molecular Biology
- Genomics
Background:
- Asthma prevalence is increasing, necessitating novel research into its pathogenesis.
- Existing research highlights the need for new scientific inquiry into asthma.
- Understanding disease mechanisms requires unbiased insights.
Purpose of the Study:
- To investigate gene expression profiles in mouse lungs with experimental asthma.
- To identify key genes and pathways involved in asthma pathogenesis.
- To explore the role of arginine metabolism in allergic airway inflammation.
Main Methods:
- Expression profiling of lung tissue from mouse models of experimental asthma.
- Utilizing different allergens and induction protocols to create asthma models.
- In situ hybridization to localize gene expression.
- Measuring enzyme activity and downstream products.
Main Results:
- Identified 6.5% of the genome with altered expression in asthmatic lungs.
- Highlighted genes involved in basic amino acid metabolism, including arginase I and II.
- Demonstrated increased arginase activity and putrescine levels in allergen-challenged lungs.
- Showed IL-4 and IL-13 induction of lung arginase activity and mRNA expression.
- Confirmed the relevance of these findings in human asthma patients.
Conclusions:
- Arginase pathway genes are significantly altered in experimental asthma.
- Arginase activity is increased in asthma and linked to allergic inflammation.
- Targeting arginine metabolism offers a potential therapeutic strategy for allergic disorders.
- Findings in mouse models translate to relevance in human asthma.
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