Genome-wide profiling of antigen-induced time course expression using murine models for acute and chronic asthma.
BACKGROUND
Asthma is a complex-trait disease caused by complicated interactions among multiple genetic and environmental risk factors. The clinical symptoms of asthma, such as periodic airway obstruction, hyperresponsiveness and mucus hypersecretion, are mediated by acute and chronic bronchial inflammation.


METHODS
To better understand the mechanisms by which allergen-induced acute inflammation leads to chronic asthma accompanied by irreversible airway remodeling, we analyzed time course transcriptional responses in the lungs of model mice that were exposed to aerosolized ovalbumin for up to 9 weeks after an initial sensitization.


RESULTS
We observed increased levels of total plasma IgE and histological changes in lung tissues from the ovalbumin-treated mice, which is consistent with the typical inflammatory phenotypes of asthma pathogenesis. Our oligonucleotide microarray analyses revealed a total of 776 differentially expressed genes induced by antigenic challenge (> or =1.5-fold change, p < 0.05). Of these genes, most of the immune-responsive genes were transiently up-regulated in the early phase of the allergen treatment (within a week) with a concomitant up-regulation of genes involved in mucus production. These genes were not differentially regulated in the mice challenged for a longer period of time (up to 6 weeks). We also identified some of the genes implicated in extracellular matrix remodeling, for which the time course expression did not necessarily coincide with the expression patterns of immune-responsive genes.


CONCLUSIONS
Our data suggest that there is a complex interregulatory genetic network associated with the structural changes that accompany the progression of the allergic inflammatory reaction in chronic asthma.
Park
Seong Gyu
SG
Center for Genome Science, National Institute of Health, Seoul, Korea.
Choi
Jung-Won
JW
Kim
Hyun jae
Hj
Roh
Gu Seob
GS
Bok
Jeong
J
Go
Min Jin
MJ
Kwack
KyuBum
K
Oh
Bermseok
B
Kim
Yeonjung
Y
D000818:Animals; D001249:Asthma / Q000235:genetics* / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D023281:Genomics / Q000379:methods; D006651:Histocytochemistry; D007073:Immunoglobulin E / Q000097:blood; D008168:Lung / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D020411:Oligonucleotide Array Sequence Analysis; D010047:Ovalbumin / Q000276:immunology* / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018418:Th2 Cells / Q000276:immunology; D014158:Transcription, Genetic; D015854:Up-Regulation
D012333:RNA, Messenger; D007073:Immunoglobulin E; D010047:Ovalbumin