ASTHMA, ALLERGIC AND IMMUNOLOGIC DISEASES COOP RES CTR

哮喘、过敏和免疫性疾病 COOP RES CTR

• 批准号: 2069714
• 负责人: Max Dale Cooper
• 金额: $ 56.27万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-08-01 至 1998-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2069714
• 关键词: asthma; cooperative study; immunoglobulin E; immunoglobulin genes

The Asthma, Allergic, and Immunologic Diseases Cooperative Research Center of the University of Alabama at Birmingham (UAB) is a multidisciplinary effort, involving faculty and staff of the clinical Departments of Medicine and Pediatrics, and the basic science Department of Microbiology. The primary focus is the elucidation of pathogenetic mechanisms operative in allerigc diseases of immune function. The Demonstration and Education Research component will focus on means to increase the effectiveness of educational interventions in improving asthma management. The BioMedical Research Component is composed of four integrated research projects designed to pursue experimental leads gained in earlier studies. As most of the investigators are actively involved in the care of patients with immunologic diseases, the program provides a working interface between basic and applied immunology. Atopic diseases result from the release of mediators of inflammation, a process associated with aggregation of high affinity receptors for lgE on the surface of mast cells (Fc-epsilon-RI). Project 1 will focus on phospholipase C-gamma1 isozymes that have been recently shown to be activated following Fc-epsilon-RI aggregation. Mechanisms of substrate hydrolysis and signal transduction will be studied. Project 2 will examine the hypothesis that susceptibility to atopic disease results from premature activation of the IgE response in the fetus. The composition of the IgE antibody repertoire will be determined as a function of ontogeny. Infants at high risk for atopic disease will be identified through recruitment of pregnant women in our allergy clinics and their cord blood IgE repertoire will be examined. Project 3 will focus on analysis of the molecular mechanisms that contribute to the immature phenotype of sIgA+ cells that are seen patients with IgA deficiency (IgAD) and in normal newborns. These cells will be purified by a newly developed combination of sorting techniques for analysis of the extent of C-mu deletion, a prerequisite for class switch recombination. The cells will also be examined for their responses to cytokines and to purified mixtures of T and B cell subpopulations. In order to gain further insight into host factors that can compensate for lgA deficiency, a mutant mouse model lacking lgA will be created. Abnormalities in thymic development may contribute to both atopy and lgA deficiency. In Project 4, the mechanism by which abnormal expression of the fas apoptosis antigen contributes to the loss of T cell tolerance in lpr mice will be studied.

哮喘、过敏和免疫疾病合作研究中心 阿拉巴马大学伯明翰分校 (UAB) 是一所多学科的大学 临床科室的教职员工的努力 医学和儿科，以及微生物学基础科学系。 主要焦点是阐明发病机制 免疫功能的过敏性疾病。示范与教育 研究部分将侧重于提高有效性的方法 改善哮喘管理的教育干预措施。生物医学 研究部分由四个综合研究项目组成 旨在追求早期研究中获得的实验线索。正如大多数 的研究人员积极参与患者的护理 免疫疾病，该程序提供了一个工作接口 基础和应用免疫学。特应性疾病是由释放的 炎症介质，一个与高浓度聚集相关的过程 肥大细胞表面 lgE 亲和受体 (Fc-epsilon-RI)。 项目 1 将重点关注磷脂酶 C-gamma1 同工酶 最近显示在 Fc-epsilon-RI 聚合后被激活。 底物水解和信号转导的机制将是 研究过。项目 2 将检验以下假设： 特应性疾病是由 IgE 反应过早激活引起的 胎儿。 IgE 抗体库的组成将是 确定为个体发育的函数。特应性高风险婴儿 我们将通过招募孕妇来识别疾病 过敏诊所及其脐带血 IgE 库将接受检查。 项目3将重点分析分子机制 导致患者出现 sIgA+ 细胞的不成熟表型 IgA 缺乏症 (IgAD) 和正常新生儿。这些细胞将是 通过新开发的分选技术组合进行纯化 分析 C-mu 缺失的程度，这是类别转换的先决条件 重组。还将检查细胞的反应 细胞因子以及 T 细胞和 B 细胞亚群的纯化混合物。在 为了进一步了解可以补偿的宿主因素 lgA缺陷，将创建缺乏lgA的突变小鼠模型。 胸腺发育异常可能导致特应性和 LGA 不足。 项目4中，异常表达的机制 fas 凋亡抗原导致 T 细胞耐受性丧失 将研究 lpr 小鼠。

项目成果

Intracellular IL-1beta is an inhibitor of Fas-mediated apoptosis.

细胞内 IL-1beta 是 Fas 介导的细胞凋亡的抑制剂。

• 发表时间: 1996
• 期刊: Journal of immunology (Baltimore, Md. : 1950)
• 作者: Tatsuta,T;Cheng,J;Mountz,JD
• 通讯作者: Mountz,JD

Increased susceptibility of fas mutant MRL-lpr/lpr mice to staphylococcal enterotoxin B-induced septic shock.

fas 突变 MRL-lpr/lpr 小鼠对葡萄球菌肠毒素 B 诱导的败血性休克的易感性增加。

• 发表时间: 1995
• 期刊: Journal of immunology (Baltimore, Md. : 1950)
• 作者: Mountz,JD;Baker,TJ;Borcherding,DR;Bluethmann,H;Zhou,T;Edwards3rd,CK
• 通讯作者: Edwards3rd,CK

Impairment of T and B cell development by treatment with a type I interferon.

• DOI: 10.1084/jem.187.1.79
• 发表时间: 1998-01-05
• 期刊: The Journal of experimental medicine
• 作者: Lin Q;Dong C;Cooper MD
• 通讯作者: Cooper MD

The mouse BP-1 gene: structure, chromosomal localization, and regulation of expression by type I interferons and interleukin-7.

小鼠 BP-1 基因：结构、染色体定位以及 I 型干扰素和白细胞介素 7 的表达调节。

• DOI: 10.1006/geno.1996.0180
• 发表时间: 1996
• 期刊: Genomics
• 影响因子: 4.4
• 作者: Wang,J;Walker,H;Lin,Q;Jenkins,N;Copeland,NG;Watanabe,T;Burrows,PD;Cooper,MD
• 通讯作者: Cooper,MD

Inhibition of superantigen-induced proinflammatory cytokine production and inflammatory arthritis in MRL-lpr/lpr mice by a transcriptional inhibitor of TNF-alpha.

通过 TNF-α 转录抑制剂抑制 MRL-lpr/lpr 小鼠中超抗原诱导的促炎细胞因子产生和炎症性关节炎。

• 发表时间: 1996
• 期刊: Journal of immunology (Baltimore, Md. : 1950)
• 作者: Edwards3rd,CK;Zhou,T;Zhang,J;Baker,TJ;De,M;Long,RE;Borcherding,DR;Bowlin,TL;Bluethmann,H;Mountz,JD
• 通讯作者: Mountz,JD