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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.