Expression profiling of genes related to asthma exacerbations.
BACKGROUND
Asthma is a chronic airway inflammatory disease; however, the molecular mechanisms that underlie asthma exacerbation are only partially understood.


OBJECTIVE
To identify gene expression signatures that reflect the acute exacerbation of asthma, we examined the differential expression of genes during asthma exacerbation and stable condition by using microarray analysis.


METHODS
The subjects were mite-sensitive asthmatic children and non-asthmatic control children. The children were divided into four groups (AE: asthma exacerbation, n=12; SA: stable asthma, n=11; IC: infected control, n=6; and NC: non-infected control, n=5). Total RNA was extracted from peripheral blood mononuclear cells and subjected to microarray analysis with Illumina Human Ref8 BeadChip arrays. Welch's t-test was performed to identify genes whose expression was altered during asthma exacerbation. Quantitative real-time RT-PCR was performed on samples collected from 43 asthmatic children and 11 control children to verify the microarray results.


RESULTS
The expression of 137/16 genes was significantly up/down-regulated during asthma exacerbation assessed by microarray analysis. Of the genes, 62 were also differentially expressed during upper respiratory infection. Many of the asthma exacerbation related genes were involved in defence responses and responses to external stimuli, but these associations disappeared after excluding the infection-related genes. Quantitative real-time RT-PCR confirmed that the genes related (S100A8 and GAS6) and unrelated to infections (CD200 and RBP7) were differentially expressed during asthma exacerbation (P<0.01).


CONCLUSIONS
Previously unidentified immune responses during asthma exacerbation may provide further clarification of the molecular mechanisms underlying asthma.
Aoki
T
T
Department of Pediatrics, Tsukuba Medical Center Hospital, Tsukuba City, Ibaraki, Japan.
Matsumoto
Y
Y
Hirata
K
K
Ochiai
K
K
Okada
M
M
Ichikawa
K
K
Shibasaki
M
M
Arinami
T
T
Sumazaki
R
R
Noguchi
E
E
D000293:Adolescent; D015703:Antigens, CD / Q000235:genetics; D001249:Asthma / Q000235:genetics* / Q000503:physiopathology*; D040502:Calgranulin B / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks / Q000235:genetics; D005796:Genes / Q000235:genetics; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D012141:Respiratory Tract Infections / Q000235:genetics; D054840:Retinol-Binding Proteins, Cellular / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation / Q000235:genetics; D000099255:Growth Arrest-Specific Protein 6
D015703:Antigens, CD; D040502:Calgranulin B; D036341:Intercellular Signaling Peptides and Proteins; D054840:Retinol-Binding Proteins, Cellular; D000099255:Growth Arrest-Specific Protein 6; C422994:RBP7 protein, human; C042739:antigens, CD200