IL-4 Signal Transduction

描述(申请人提供)：细胞因子是免疫反应的重要调节剂，免疫反应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发现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寡核苷酸阵列来解决这个问题，以定义由这些细胞因子激活的不同信号通路如何调控基因转录。这项工作发现了由IL-4诱导的新基因。我们建议确定这些基因编码的蛋白质是否对IL-4功能重要。此外，我们将扩展我们的微阵列工作，以确定IL-4如何激活不同的信号分子，以协调基因表达的调节。最后，最近的数据表明，编码这些信号分子中的一些分子的基因多态与哮喘或特应性有关。我们将确定这些等位基因变异是否会导致IL-4诱导的基因表达的变化。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。

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.