SJOGRENS SYNDROME SALIVARY GLAND AND APOPTOSIS

干燥综合征唾液腺和细胞凋亡

• 批准号: 6176008
• 负责人: HOWARD DANG
• 金额: $ 22.32万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-04-01 至 2002-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6176008
• 关键词: Adenoviridae; BCL2 gene /protein; RNase protection assay; Sjogren's syndrome; acinar cell; apoptosis; autoimmune disorder; biological signal transduction; biopsy; clinical research; cysteine endopeptidases; cytokine; enzyme inhibitors; gene expression; human subject; immunocytochemistry; laboratory rat; parotid gland; pathologic process; salivary glands; submandibular gland; tissue /cell culture; transfection /expression vector; western blottings; xerostomias

Programmed cell death (PCD) or apoptosis is a highly regulated physiological process which eliminates specific cells from an organism. PCD plays a critical role during embryonic development but is present throughout life. Unregulated or abnormal apoptosis can lead to disease or unwanted tissue destruction. Many tissues, including the salivary gland, express the surface molecule called Fas (CD95) which can deliver an apoptotic signal. Sjogren's syndrome is an autoimmune disease of the exocrine glands that leads to xerostomia and xeropthalmia. Many of the glandular features show evidence of apoptotic destruction. The long term objective of this study is to elucidate the mechanism leading to PCD in the Sjrgren's syndrome salivary gland. The Specific Aims are: 1) Study in situ Fas-mediated PCD, bcl-2 family protein expression, the affects of cytokines in the rat salivary gland; 2) Induce with cytokines Fas ligand and bcl-2 family protein expression in the salivary cell lines, (HSY, SMG C6 and SMG C10); 3) determine the role of proapoptotic caspases in rat and human salivary glands; 4) detect in the Sjrgren's syndrome salivary gland abnormal changes in bcl-2 family member expression. Studies will include immunochemical staining techniques and Western blot Rat parotid and submandibular glands will be cannulated. Cytokines or ant-Fas antibody will be injected into the gland and assessed for apoptosis and PCD associated proteins. Salivary gland cell lines will be cultured with cytokines and studied for apoptosis, Fas-L expression, and bcl-2 family member expression. Gene transfer studies will be performed in vivo and in vitro to regulate Fas ligand and bcl-2 family prtein expression. Caspase inhibitors will be used to identify specific proteases during apoptosis. Biopsy material from patents with Sjogren's syndrome will be immunostained for bcl-2 family member expression.

程序性细胞死亡（PCD）或凋亡是一个高度调节的生理过程，可消除从生物体中的特定细胞。 PCD在胚胎开发过程中起着至关重要的作用，但一生都存在。 未受管制或异常的凋亡会导致疾病或不必要的组织破坏。包括唾液腺在内的许多组织表达了称为FAS（CD95）的表面分子，该表面可以传递凋亡信号。 Sjogren综合征是一种外分泌腺体的自身免疫性疾病，导致血清症和眼科疾病。 许多腺特征都显示出凋亡破坏的证据。 这项研究的长期目标是阐明导致SJ Rgren综合征唾液腺中PCD的机制。具体目的是：1）研究原位FAS介导的PCD，Bcl-2家族蛋白表达，大鼠唾液腺中细胞因子的影响； 2）在唾液细胞系中用细胞因子FAS配体和Bcl-2家族蛋白表达诱导（HSY，SMG C6和SMG C10）； 3）确定凋亡性胱天蛋白酶在大鼠和人类唾液腺中的作用； 4）检测Bcl-2家族成员表达中SJ RGREN综合征唾液腺异常变化。研究将包括免疫化学染色技术和蛋白质印迹大鼠腮腺和下颌下腺。 细胞因子或ANT-FAS抗体将被注射到腺体中，并评估凋亡和PCD相关蛋白。唾液腺细胞系将用细胞因子培养，并研究用于细胞凋亡，FAS-L表达和BCL-2家族成员表达。 基因转移研究将在体内和体外进行，以调节FAS配体和Bcl-2家族prtein表达。 caspase抑制剂将用于识别细胞凋亡期间的特定蛋白酶。 Sjogren综合征专利的活检材料将被免疫染色，以用于Bcl-2家庭成员表达。