CONTROL OF INTERLEUKIN-2 IN SJOGREN'S SYNDROME

干燥综合征(SS)的特征是淋巴细胞的浸润性 唾液腺会导致各种牙科并发症。这 该项目的重点是涉及SS的IL-2生物学中的分子异常 T细胞。SS患者外周血中的T淋巴细胞对 有丝分裂刺激和抗原刺激，而T淋巴细胞则渗入 SS唾液腺活跃地产生IL-2。其中一些是更古老的 基于细胞激活标记的观察；其他是最近的发现 从我们自己的实验室测量转录因子或使用PCR 在SS唾液腺组织中扩增。当前的具体目标 以下是用来进一步分析信号异常的 与10月1日转录因子缺陷相关的转导 IL-2基因激活所必需的，以继续我们的细胞因子分析 利用聚合酶链式反应，并开发SS的新的治疗方法。 具体目标： 1.与同源DNA序列结合的核蛋白的表达 在IL-2基因启动子区域(转录因子)将被评估 通过电泳迁移率改变分析。这一信号事件是 可能是这条通路的最远端。因此，异常情况 将支持我们的假设，即早期信号缺陷 钙有助于减少IL-2的生物合成。 2.将在SS中研究编码IL-2基因的特定mRNAs 用聚合酶链式反应检测唾液腺。炎性细胞因子的表达 如SS组织中的IL-2可以解释这种强烈的 淋巴细胞渗入和组织破坏。 3.IL-2生物合成的正常化及其表达 参与调节IL-2基因的蛋白质，将被尝试 使用已知可以增强T细胞激活的药物。阿司匹林类药物 提高L-2产量和早期和晚期信号事件将 学习。

Sjogren's syndrome (SS) is characterized by lymphocytic infiltration of the salivary glands leading to a variety of dental complications. This project focuses on molecular abnormalities in IL-2 biology involving SS T cells. T lymphocytes from SS peripheral blood are hyporesponsive to mitogenic and antigenic stimuli, whereas T lymphocytes infiltrating the SS salivary glands actively produce IL-2. Some of these are older observations based on cell activation markers; others are recent findings from our own laboratory measuring transcription factors or using PCR amplification in SS salivary gland tissue. The current specific aims which follow are designed to further analyze abnormalities of signal transduction in relation to a defect in the Oct. 1 transcription factor necessary for IL-2 gene activation, to continue our analysis of cytokine profiles using PCR, and to develop new therapeutic modalities for SS. Specific aims: 1. The expression of nuclear proteins binding to cognate DNA sequences in the IL-2 gene promoter region (transcription factors) will be assessed by electrophoretic mobility shift assay. This signaling event is putatively the most distal in the pathway. Therefore, abnormalities detected would support our hypothesis that an early signaling defect in calcium contributes to the reduced biosynthesis of IL-2. 2. Specific mRNAs for the gene encoding IL-2 will be studied in SS salivary glands using the PCR. Demonstration of inflammatory cytokines such as IL-2 in SS tissues could provide an explanation for the intense lymphocytic infiltration and tissue destruction. 3. Normalization of IL-2 biosynthesis, as well as the expression of proteins involved in the regulation of the IL-2 gene, will be attempted using drugs known to enhance T cell activation. Aspirin-like drugs that enhance L-2 production and both early and late signaling events will be studied.