2004 Fiscal Year Final Research Report Summary
Internal factors in inflammatory respiratory diseases
| Project/Area Number |
14370193
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | HOKKAIDO UNIVERSITY |
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Principal Investigator |
NASUHARA Yasuyuki Hokkaido Univ., Hokkaido Univ.Hosp., Assis.Prof., 病院, 講師 (30322811)
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| Co-Investigator(Kenkyū-buntansha) |
HIZAWA Nobuyuki Hokkaido Univ., Grad.School of Med., Asso.Prof., 大学院・医学研究科, 助教授 (00301896)
BETSUYAKU Tomoko Hokkaido Univ., Hokkaido Univ.Hosp., Assis.Prof., 病院・講師 (60333605)
NISHIMURA Masaharu Hokkaido Univ., Grad.School of Med., Prof., 大学院・医学研究科, 教授 (00208224)
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| Project Period (FY) |
2002 – 2004
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| Keywords | bronchial asthma / gene polymorphism / FCεR1β / PAI1 / pulmonary emphysema / epithelial cell / IL-8 / MIP-1α |
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| Research Abstract |
We performed the study to examine whether the 109C/T FcεRIβ promoter polymorphism influences the genetic effects of the functional polymorphism (4G/5G) at the PAI-1 promoter region on asthma susceptibility using a case-control analysis. Individuals homozygous for both the FcεRIβ-109T allele and the PAI-1 5G allele had a reduced susceptibility to asthma ; the odds ratio associated with the PAI-1 5G/5G genotype was 1.14 (p=0.72) in carriers of the FcεRIβ-109C allele, 0.29 (p=0.00023) in carriers of the FcεRIβ-109T/T genotype compared to individuals carrying the FcεRIβ-109T/T genotype and the PAI-1 4G allele. The regression model also showed an interaction between FcεRIβ and PAI-1 genotypes on asthma (p for interaction=0.0017). The present findings suggest a synergistic interaction between FcεRIβ and PAI-1 genes in asthma susceptibility.
In the present study, we first quantified cytokine mRNA in human bronchiolar epithelial cells and macrophages obtained using laser-capture microdissection and explored the relationship with early-stage COPD. Only in bronchiolar epithelial cells were IL-8, MIP-1α, and MCP-1 mRNA levels higher in smokers with airflow limitation and/or emphysema than those in never smokers or smokers without either airflow limitation or emphysema. cDNA array further revealed the overexpression of CC chemokine receptor 2 in bronchiolar epithelial cells from smokers with airflow limitation and/or emphysema. This study supports the role of bronchiolar epithelium as the source of increased inflammatory cytokine levels in the early development of COPD and also demonstrates the potential use of laser-capture microdissection, combined with reverse transcriptase-polymerase chain reaction and cDNA microarrays, to investigate functional profiles of indivisual structural and inflammatory cells in human lungs.
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