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Internal factors in inflammatory respiratory diseases

炎症性呼吸道疾病的内部因素

基本信息

批准号：
14370193
负责人：
NASUHARA Yasuyuki
金额：
$ 8.83万
依托单位：
HOKKAIDO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370193/
关键词：
bronchial asthma gene polymorphism FCεR1β PAI1 pulmonary emphysema epithelial cell IL-8 MIP-1α アデノウィルス EBウィルス MIF アトピー喘息アデノウイルスウイルスEB MOC TARC

项目摘要

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.

我们采用病例对照分析的方法研究了109C/T FcεRIβ启动子区功能多态(4G/5G)是否影响哮喘易感性的遗传效应。携带FcεRIβ-109T等位基因和PAI-1 5G等位基因的个体与携带FcεRIβ-109C等位基因和携带FcεRIβ-109T/T等位基因的个体相比，携带FcεRIβ-109T/T和FcεRIβ-109T/T等位基因的个体与携带FcεRIβ-109T/T和PAI-1 4G等位基因的个体相比，其患哮喘的易感性降低。回归模型还显示Fc、ε、RI、β和PAI-1基因对哮喘存在交互作用(p=0.0017)。目前的研究结果提示，Fc、ε、RI、β和PAI-1基因在哮喘易感性中存在协同作用。在本研究中，我们首先定量了激光捕获显微切割获得的人细支气管上皮细胞和巨噬细胞中的细胞因子基因，并探讨了与早期慢性阻塞性肺疾病的关系。有气流受限和/或肺气肿的吸烟者仅细支气管上皮细胞IL-8、MIP1和α的表达水平高于不吸烟者和无气流受限或肺气肿的吸烟者。基因芯片进一步揭示了气流受限和/或肺气肿的吸烟者细支气管上皮细胞中CC趋化因子受体2的过度表达。这项研究支持细支气管上皮在慢性阻塞性肺疾病早期发展中作为炎性细胞因子水平升高的来源的作用，并展示了激光捕获显微解剖结合逆转录聚合酶链式反应和cDNA微阵列的潜在用途，以研究人类肺部内部结构和炎性细胞的功能图谱。