Microarray profile of differentially expressed genes in a monkey model of allergic asthma
1 Department of Allergy, Schering-Plough Research Institute, 2015 Galloping Hill Rd, Kenilworth, NJ 07033, USA
2 Department of Biostatistics, Schering-Plough Research Institute, 2015 Galloping Hill Rd, Kenilworth, NJ 07033, USA
3 Department of Bioinformatics, Schering-Plough Research Institute, 2015 Galloping Hill Rd, Kenilworth, NJ 07033, USA
4 DNAX Research Institute, 901 California Ave, Palo Alto, CA 94304, USA
Genome Biology 2002, 3:research0020-research0020.13 doi:10.1186/gb-2002-3-5-research0020Published: 11 April 2002
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.
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.
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.