Microarray profile of differentially expressed genes in a monkey model of allergic asthma.
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.


CONCLUSIONS
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.
Zou
Jun
J
Department of Allergy, Schering-Plough Research Institute, 2015 Galloping Hill Rd, Kenilworth, NJ 07033, USA. jun.zou@spcorp.com
Young
Simon
S
Zhu
Feng
F
Gheyas
Ferdous
F
Skeans
Susan
S
Wan
Yuntao
Y
Wang
Luquan
L
Ding
Wei
W
Billah
Motasim
M
McClanahan
Terri
T
Coffman
Robert L
RL
Egan
Robert
R
Umland
Shelby
S
D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology; D017165:Ascaris suum / Q000276:immunology; D001249:Asthma / Q000235:genetics* / Q000276:immunology*; D016000:Cluster Analysis; D004195:Disease Models, Animal; D020869:Gene Expression Profiling / Q000379:methods* / Q000706:statistics & numerical data; D006967:Hypersensitivity / Q000235:genetics / Q000276:immunology; D008252:Macaca fascicularis; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods* / Q000706:statistics & numerical data
D000947:Antigens, Helminth