| Project/Area Number |
18591097
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
膠原病・アレルギー・感染症内科学
|
|---|
| Research Institution | University of Tsukuba |
|---|
Principal Investigator |
NOGUCHI Emiko University of Tsukuba, Graduate School of Comprehensive Human Sciences, Assistant Professor (40344882)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
UCHIDA Kazuhiko University of Tsukuba, Graduate School of Comprehensive Human Sciences, Assistant Professor (90211078)
|
|---|
| Project Period (FY) |
2006 – 2007
|
| Project Status |
Completed (Fiscal Year 2007)
|
| Budget Amount *help |
¥4,010,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥510,000)
Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
|
|---|
| Keywords | asthma / microarray / proteome |
|---|
| Research Abstract |
Asthma is the most common chronic disorder in childhood, and asthma exacerbation is an important cause of childhood morbidity and hospitalization. Allergic responses are known to be biased toward T-helper type 2 in asthmatics; however, the pathogenesis of asthma is not simple, and our understanding of the disease mechanism remains incomplete. The aim of the present study was to identify gene/protein expression signatures that reflect acute exacerbation of asthma.
Blood was taken twice from pediatric asthmatic patients, once during asthma exacerbation and once during a stable period. Blood was also taken from healthy children as a control. Total RNA was extracted from peripheral blood mononuclear cells and subjected to microarray analysis with a Takara IntelliGene HS Human Expression CHIP and an Illumina Sentrix Human-6 Expression BeadChip. Paired t-test was performed to identify genes showing altered expression during asthma exacerbation. Quantitative real-time reverse transcription-pol
… More
ymerase chain reaction was performed with 48 asthmatic children to verify the microarray results. Pathway analysis was performed with IPA version 5.0 software. Expression of 26/3 genes was significantly up/down-regulated during asthma exacerbation by microarray analysis. Many of the differentially expressed genes were involved in defense responses against pathogens and interferon induction. In pathway analysis, tumor necrosis factor and interferon gamma were centered with the highest connections in the network. Tumor necrosis factor is associated with asthma exacerbation as a potent pro-inflammatory cytokine. Interferon gamma is involved in numerous immune interactions during viral infection and contributes to antiviral mechanisms. Expression levels of IFN-related genes were higher in rhinovirus viremia positive-group than in negative-group (P<0.05).
Protein expression profiles of plasma during asthma exacerbation were analyzed by 2-DE, and 49 spots were differentially expressed during asthma exacerbation. Thirty-eight of the spots were successfully identified by MALD-TOF MS. Proteins up-or down-regulated during asthma exacerbation were involved in responses to stress and pathogens, in the complement and coagulation cascades, and in acute phase responses. Among the differentially expressed proteins, up-regulation of alpha-1-antitrypsin and complement component C7 was confirmed by nephelometry and ELISA. Our present results suggest that IFN-related genes/protease inhibitors and complement components may be involved in asthma exacerbation. Less
|
