Internal factors in inflammatory respiratory diseases

本研究采用病例对照分析方法，探讨PAI-1基因启动子区109 C/T FcεRIβ基因多态性是否影响PAI-1基因启动子区4G/5G功能多态性对哮喘易感性的遗传效应。FcεRIβ-109T等位基因和派-1 5G等位基因纯合子个体对哮喘的易感性降低;派-1 5G/5G基因型的优势比为1.14（p=0.72）在FcεRIβ-109 C等位基因携带者中，与携带Fc ε RI β-109 T/T基因型和派-1 4G等位基因的个体相比，Fcε RI β-109 T/T基因型携带者中PAI-1 4G的表达为0.29（p=0.00023）。回归模型还显示FcεRIβ和派-1基因型在哮喘发病中存在交互作用（交互作用p =0.0017）。本研究首次采用激光捕获显微切割技术，定量检测了人细支气管上皮细胞和巨噬细胞中细胞因子mRNA的表达，并探讨了其与早期COPD的关系。只有在细支气管上皮细胞中，吸烟者伴气流受限和/或肺气肿的IL-8、MIP-1α和MCP-1 mRNA水平高于从不吸烟者或吸烟者不伴气流受限或肺气肿的细支气管上皮细胞。cDNA微阵列进一步揭示了CC趋化因子受体2在吸烟者气流受限和/或肺气肿的细支气管上皮细胞中的过表达。这项研究支持支气管上皮细胞作为COPD早期发展中炎性细胞因子水平增加的来源的作用，并证明了激光捕获显微切割结合逆转录酶-聚合酶链反应和cDNA微阵列的潜在用途，以研究人类肺部个体结构和炎性细胞的功能概况。

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.