IL-4 Signal Transduction

IL-4信号转导

• 批准号: 7208085
• 负责人: Paul B Rothman
• 金额: $ 31.47万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-04-15 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7208085
• 关键词: Address; Allergic; Apoptosis; Asthma; B Cell Proliferation; B cell differentiation; B-Lymphocytes; Binding; Cell physiology; Cells; Cellular biology; Data; Disease; Endothelium; Enzymes; Event; Extrinsic asthma; Gene Activation; Gene Expression; Gene Expression Regulation; Genes; Genetic Polymorphism; Genetic Transcription; Genetic Variation; Heavy-Chain Immunoglobulins; Human; Hypersensitivity; IgE; IgG1; IgG4; Immune response; Immunoglobulin Class Switching; Inflammatory; Interleukin 4 Receptor; Interleukin-13; Interleukin-4; JAK3 gene; Lead; Link; MHC Class II Genes; Mediating; Microarray Analysis; Molecular; Mus; Oligonucleotide Microarrays; PTPN6 gene; Pathway interactions; Phosphotransferases; Play; Process; Proteins; Regulation; Research; Research Personnel; Role; STAT6 gene; Signal Pathway; Signal Transduction; Signaling Molecule; T-Lymphocyte; Therapeutic Intervention; Work; atopy; cytokine; novel; receptor; response

DESCRIPTION (provided by applicant): Cytokines are important modulators of the immune response that underlies the inflammatory process in atopic forms of asthma. IL-4 and IL-13 are important cytokines for the regulation of these asthmatic immune responses. Work over the past ten years has identified many signaling molecules activated by these cytokines and outlined the basic mechanisms by which binding of these cytokines to their receptor leads to this activation. What remains unknown is how these signaling events are integrated by the cell into a biologic response. We have begun to address this question by using Affymetrix oligonucleotide arrays to define how different signaling pathways activated by these cytokines regulate gene transcription. This work has identified novel genes induced by IL-4. We propose to determine if the proteins encoded for by these genes are important for IL-4 function. In addition, we will extend our work with microarrays to determine how activation of different signaling molecules by IL-4 converges in a coordinated regulation of gene expression. Finally, recent data suggest that polymorphisms in the genes encoding some of these signaling molecules are associated with either asthma or atopy. We will determine if these allelic variants lead to alteration in IL-4 induced gene expression. Together, these results will provide investigators in asthma research important information regarding the function of these cytokines.

描述（由申请人提供）：细胞因子是免疫反应的重要调节剂，是特应性哮喘炎症过程的基础。IL-4和IL-13是调节哮喘免疫反应的重要细胞因子。过去十年的工作已经确定了许多由这些细胞因子激活的信号分子，并概述了这些细胞因子与其受体结合导致这种激活的基本机制。目前尚不清楚的是这些信号事件是如何被细胞整合成生物反应的。我们已经开始通过使用Affymetrix寡核苷酸阵列来确定这些细胞因子激活的不同信号通路如何调节基因转录来解决这个问题。本研究发现了IL-4诱导的新基因。我们打算确定这些基因编码的蛋白质是否对IL-4的功能很重要。此外，我们将利用微阵列扩展我们的工作，以确定IL-4如何激活不同的信号分子，从而协调调节基因表达。最后，最近的数据表明，编码这些信号分子的基因多态性与哮喘或特应性有关。我们将确定这些等位基因变异是否导致IL-4诱导的基因表达改变。总之，这些结果将为哮喘研究人员提供有关这些细胞因子功能的重要信息。