EFFECT OF INFLAMMATORY MEDIATORS ON MUCIN GENE EXPRESSION

呼吸道分泌物过多是呼吸道的主要原因。 阻塞性哮喘、慢性支气管炎和囊性纤维化。一个 即刻超敏反应和急性超敏反应的多种介质 研究表明，炎症可以增加呼吸道分泌物。 粘蛋白糖蛋白。关于这一影响的数据很少。 炎症介质对呼吸道粘蛋白基因表达的影响 这项研究的目标是确定炎症的影响和 呼吸道粘膜炎症的已知介质对呼吸道的影响 粘蛋白基因的表达。这些研究利用呼吸道上皮细胞 来自人类受试者、实验动物和人类的细胞 细胞系。聚合酶链式反应用于粘蛋白的定量 利用先前发表的粘蛋白设计的聚合酶链式反应探针的消息 基因结构。这一数据与分泌研究相关，使用 一种针对呼吸道粘蛋白的酶联免疫吸附试验。内毒素、肿瘤坏死因子α、白介素I和 已发现IL-6能够诱导血管内皮细胞粘蛋白基因表达 呼吸道上皮细胞。细胞内事件涉及到的 这一过程正在调查中。蛋白激酶C的激活 似乎与肿瘤坏死因子诱导RNA中的MUC-2有关。 目前正在进行研究，以评估NFKB在这方面的作用 进程。此外，已发现II-10可抑制肿瘤坏死因子诱导的 粘蛋白过度分泌和研究目前正在进行中，以确定 IL-10的作用机制。这个项目可能会考虑到新的 洞察细胞因子对上皮细胞基因表达的调控。

Excessive respiratory secretions are a major cause of the airway obstruction in Asthma, Chronic Bronchitis and Cystic Fibrosis. A variety of mediators of immediate hypersensitivity and of acute inflammation have been shown to increase secretion of respiratory mucin glycoprotein. Little data is available on the effect of mediators of inflammation on gene expression of respiratory mucins. The goal of this study is to define the effect of inflammation and of the known mediators of respiratory mucosal inflammation on respiratory mucin gene expression. These studies utilize respiratory epithelial cells from human subjects and experimental animals and from a human cell line. Polymerase chain reaction is used to quantitate mucin message utilizing PCR probes designed from previously published mucin gene structure. This data is correlated with secretory studies using an Elisa specific for respiratory mucin. Endotoxin, TNFalpha, IL-I and IL-6 have been found capable of inducing mucin gene expression in respiratory epithelial cells. The intracellular events involved in this process are under investigation. Activation of ProteinKinase C appears to be involved in the induction of MUC-2 in RNA by TNF. Studies are currently underway to evaluate the role of NFKB in this process. In addition II--10 has been found to inhibit TNF induced mucin hypersecretion and studies are currently underway to determine the mechanism of the IL-10 effect. This project may allow for new insight into cytokine modulation of epithelial cell gene expression.