Anti-Inflammatory Approaches

抗炎方法

• 批准号: 9111823
• 负责人: TERRY B. STROM
• 金额: $ 6.96万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至 2017-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9111823
• 关键词: Abate; Acute-Phase Proteins; Address; Allogenic; Allografting; Anti-Inflammatory Agents; Anti-inflammatory; Antithymoglobulin; Base Sequence; Biological Assay; Biopsy; Blinded; Blood; Blood Cells; Blood specimen; CD4 Positive T Lymphocytes; CD8B1 gene; Cells; Childhood; Chimerism; Clinical Trials; Code; Custom; Cytoprotective Agent; Data; Defect; Development; Diagnosis; Early treatment; Equilibrium; Frequencies; Future; Gene Expression; Genes; Genetic Transcription; Goals; Helper-Inducer T-Lymphocyte; Housing; Human; Immunity; Individual; Inflammation; Inflammatory; Instruction; Kidney; Kidney Transplantation; Laboratories; Leukocytes; Logic; Lymphopenia; Macaca fascicularis; Macaca mulatta; Measures; Methods; Modeling; Molecular Profiling; Monitor; Monkeys; Mus; Natural Killer Cells; Organ Transplantation; Pan Genus; Patients; Phenotype; Polymerase Chain Reaction; Protein C Inhibitor; Proteins; Publishing; Reagent; Regulatory T-Lymphocyte; Replacement Therapy; Reporting; Resistance; Reverse Transcriptase Polymerase Chain Reaction; Ribosomal RNA; Role; Sampling; Serine Protease; Specimen; T memory cell; T-Lymphocyte; T-Lymphocyte Subsets; Techniques; Time; Tissue Sample; Tissues; Transcript; Translating; Transplant Recipients; Transplantation; United States National Institutes of Health; Work; allograft rejection; base; cell type; cytokine; design; in vivo Model; interest; islet; kidney allograft; macrophage; man; molecular phenotype; monocyte; novel; peripheral blood; response; treatment duration

PROJECT SUMMARY (See instructions): Our recent data show that cynomolgus transplant recipients are resistant to the induction of chimerism and transplant tolerance until the pro-inflammatory state that arises in the peri-transplant period and continues for weeks to months thereafter abates. Projects 1 and 2 place heavy emphasis upon the role of inflammation in influencing the allograft response toward or away from transplant tolerance. In accordance with this logic, Core B will interact with all of the Project 1 and 2 in vivo models, by monitoring and characterizing the state of inflammation and immunity via QRT-PCR in the cynomolgus allograft recipients. Using a panel of custom made reagents crafted for use in cynomolgus monkeys and a powerful pre-amplification technique, we can assess transcription of over 65 genes in a small tissue sample. Going forward we will further develop a single cell PCR method to provide detailed information about the frequency of T cell subsets in recipient blood or tissues. The goal is to favorably tilt the balance of immunity toward allograft protection and tolerance by controlling adverse inflammation. T alpha1 antitrypsin (AAT), an acute phase reactant and serine protease blocker is a potential agent for achieving such balance. It has been given safely as replacement therapy to patients with the AAT gene defect. This protein possesses interesting anti-inflammatory and anti-thrombotic effects. It is a potent islet cytoprotectant and although lacking direct effects upon T cells promotes T cell tolerance. This and other novel agents will be characterized in Core B for use in the Project 1 and 2 models.

项目摘要（请参阅说明）： 我们最近的数据表明，cynomolgus移植受者具有抗嵌合和移植耐受性的抵抗力，直到在移植期间出现的促炎状态，此后数周至数月暂停。项目1和2强调炎症在影响移植耐受性的同种异体移植反应中的作用。根据这种逻辑，Core B将通过监测和表征通过cynomolgus同种异体移植者中的QRT-PCR来监测和表征炎症和免疫的状态，与所有项目1和2个体内模型相互作用。使用一组定制的试剂，该试剂精心用于cynomolgus猴子和强大的预扩增技术，我们可以评估小组织样品中65多种基因的转录。展望未来，我们将进一步开发一种单细胞PCR方法，以提供有关受体血液或组织中T细胞子集频率的详细信息。 目的是通过控制不良炎症来使对同种异体移植保护和耐受性的免疫力平衡。 T alpha1抗胰蛋白酶（AAT），急性相反应物和丝氨酸蛋白酶阻滞剂是实现这种平衡的潜在药物。已将其作为替代疗法的AAT基因缺陷患者的替代疗法。该蛋白具有有趣的抗炎和抗栓性作用。它是一种有效的胰岛细胞保护剂，尽管对T细胞缺乏直接影响会促进T细胞耐受性。该新型代理将在核心B中进行表征，以用于项目1和2模型。