Polymorphic Cytokine Responses to Inflammation

多态性细胞因子对炎症的反应

• 批准号: 6731074
• 负责人: TERRI A SIMPSON
• 金额: $ 8.71万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-05-01 至 2006-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6731074
• 关键词: adolescence (12-20); adult respiratory distress syndrome; caucasian American; clinical research; cytokine; cytokine receptors; enzyme linked immunosorbent assay; gene expression; genetic polymorphism; human genetic material tag; human middle age (35-64); human subject; immunity; inflammation; interleukin 1; lipopolysaccharides; polymerase chain reaction; single nucleotide polymorphism; tissue /cell culture; young adult human (21-34)

DESCRIPTION (provided by applicant): Although mortality remains high in patients with acute respiratory distress syndrome (ARDS), an inflammatory lung condition, mystery remains about who develops ARDS. Pro-inflammatory (Interleukin-1beta) (IL-1beta) and anti-inflammatory (Interleukin-1 receptor antagonist) (IL-1ra) cytokine proteins influence lung injury, so the termination of genetic variations (polymorphisms) in these proteins before and after inflammatory responses might unveil which patients are most susceptible to ARDS. A quasi-experimental in vitro laboratory-based design is proposed to determine whether, in blood obtained from a convenient, anonymized sample of 140 healthy White volunteers of North American ethnic descent, cytokine protein levels of IL-1/a and IL-1ra differ before (constitutive) and after (inducible) lipopolysaccharide (LPS) stimulation), according to Interleukin-1B (IL-1B) and Interleukin-1 receptor antagonist (IL-1RN) genetic polymorphisms at specific chromosomal loci. Specific aims are to determine whether differences in constitutive and inducible cytokine protein levels are because the person carries any polymorphism, a specific polymorphism, or a combination of polymorphisms. An understanding of molecular phenomena that initiate biological inflammatory processes would offer the investigator an opportunity to learn immunologic and genetic assay techniques for genotyping and DNA microarray analysis to further study genetic susceptibility to ARDS. Cell culture supernatant from peripheral blood mononuclear cells without (constitutive) and with (inducible) LPS stimulation will be analyzed for IL-1a and IL-lra levels. Because IL-1beta may be higher during the luteal phase of the menstrual cycle, serum progesterone and 17beta-a estradiol will be analyzed in women as a potential covariate. DNA will be extracted and analyzed for IL- 1B and IL-1RN polymorphisms. Repeated measures (constitutive and inducible) of cytokine protein production (IL-1beta and IL-lra) will be analyzed according to the carrier status, chromosomal location of the polymorphism, and selected combinations of IL-1B and IL-IRN gene interactions.

描述（由申请人提供）：尽管急性呼吸遇险综合征（ARDS）的患者死亡率仍然很高，炎症性肺部疾病，但仍然存在关于谁发展ARDS的神秘感。促炎（Iltleukin-1Beta）（IL-1BETA）和抗炎（介绍（Iltleukin-1受体拮抗剂）（IL-1RA）细胞因子蛋白会影响肺损伤，因此在这些炎症反应中的遗传变异（多晶型）终止可能是在炎症反应前后的遗传变异（多态性），这可能是在炎症反应之前和未释放的患者。提出了一种准实验性的基于实验室的设计，以确定从北美族裔下降的140名健康白人志愿者中获得的血液中，IL-1/A和IL-1RA的细胞因子蛋白水平在（组成型）和（诱导的）脂肪性（lpopoly-carys）刺激（lpsy-cary-cary-carluide（LPS）相互作用）中，相互作用（符合）相互作用（根据特定染色体基因座的受体拮抗剂（IL-1RN）遗传多态性。具体目的是确定构成性和诱导性细胞因子蛋白水平的差异是因为该人携带任何多态性，特定的多态性或多态性的组合。对启动生物炎症过程的分子现象的理解将为研究者提供一个学习免疫和遗传测定技术的机会，用于基因分型和DNA微阵列分析，以进一步研究对ARDS的遗传易感性。将分析IL-1A和IL-LRA水平的细胞培养上清液，没有（组成型）和（可诱导）LPS刺激（可诱导）LPS刺激。由于在月经周期的黄体阶段IL-1Beta可能更高，因此将在女性中分析血清孕酮和17beta-A雌二醇作为潜在的协变量。 DNA将提取并分析IL-1B和IL-1RN多态性。将根据载体状态，多态性的染色体位置以及IL-1B和IL-IRN基因相互作用的选定组合分析细胞因子蛋白产生（IL-1BETA和IL-LRA）的重复测量（IL-1BETA和IL-LRA）。