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Microarray profile of differentially expressed genes in a monkey model of allergic asthma
- Zou, Jun, Young, Simon, Zhu, Feng, Gheyas, Ferdous, Skeans, Susan, Wan, Yuntao, Wang, Luquan, Ding, Wei, Billah, Motasim, McClanahan, Terri, Coffman, Robert L, Egan, Robert, Umland, Shelby
- Genome biology 2002 v.3 no.5 pp. 439
- Ascaris suum, allergens, antioxidant activity, asthma, breathing, bronchoconstriction, chemokines, cluster analysis, complementary DNA, disease models, gene expression, gene expression regulation, genes, hypersensitivity, interleukin-4, lungs, microarray technology, monkeys, quantitative polymerase chain reaction
- BACKGROUND: Inhalation of Ascaris suum antigen by allergic monkeys causes an immediate bronchoconstriction and delayed allergic reaction, including a pulmonary inflammatory infiltrate. To identify genes involved in this process, the gene-expression pattern of allergic monkey lungs was profiled by microarrays. Monkeys were challenged by inhalation of A. suum antigen or given interleukin-4 (IL-4) treatment; lung tissue was collected at 4, 18 or 24 h after antigen challenge or 24 h after IL-4. Each challenged monkey lung was compared to a pool of normal, unchallenged monkey lungs. RESULTS: Of the approximately 40,000 cDNAs represented on the microarray, expression levels of 169 changed by more than 2.5-fold in at least one of the pairwise probe comparisons; these cDNAs encoded 149 genes, of which two thirds are known genes. The largest number of regulated genes was observed 4 h after challenge. Confirmation of differential expression in the original tissue was obtained for 95% of a set of these genes using real-time PCR. Cluster analysis revealed at least five groups of genes with unique expression patterns. One cluster contained genes for several chemokine mediators including eotaxin, PARC, MCP-1 and MCP-3. Genes involved in tissue remodeling and antioxidant responses were also identified as regulated by antigen and IL-4 or by antigen only. CONCLUSION: This study provides a large-scale profile of gene expression in the primate lung following allergen or IL-4 challenge. It shows that microarrays, with real-time PCR, are a powerful tool for identifying and validating differentially expressed genes in a disease model.