MECHANISM OF SERUM AMYLOID A PROTEIN SYNTHESIS

血清淀粉样蛋白A(SAA)与反应性淀粉样变性有关 由于慢性感染和炎症性疾病 类风湿性关节炎、肉芽肿性肠病或骨髓炎。它是 也与家族性地中海热(FMF)有关，偶尔 在有FMF家族的无症状个体中。在反应性淀粉样变性中， 降解物AA蛋白组成的淀粉样纤维沉积 多态血清淀粉样蛋白A的产物，可出现在多个 导致器官功能障碍的器官。尽管病原学或病原学 对这一过程的机制还不完全了解， 慢性炎症条件下相关蛋白SAA的生物合成 情况很明显。一连串的分子事件涉及 炎症过程中释放的细胞因子，如慢性 感染和类风湿性关节炎，触发SAA的过度表达， 在受继发性或非传染性疾病影响的组织中发现淀粉样纤维的前体 反应性淀粉样变性..了解细胞因子的激活机制 SAA的异常表达可能提供有关 SAA相关疾病的发病机制。据推测，增加了 慢性激活因子诱导SAA基因表达的研究 炎症是一个主要的分子事件，它触发了观察到的 致病条件。 为了阐明导致基因过度表达的分子事件 SAA在慢性炎症状态下，我们打算追求以下几点 目的：1)一种新的细胞因子诱导因子--SIF的特性 炎症因子，2)不同炎症细胞因子在SAA中的作用 肝外细胞中SIF的表达3)急性加重期SIF的表达模式 4)IL-1诱导的核因子的相互作用 5)应力强度因子的结构分析。身份识别和 细胞因子的表征及其与顺式作用的相互作用 SAA基因的元件将通过凝胶迁移率改变分析来研究， 竞争分析，抑制剂的使用，共转染分析和位点- 定向诱变。这项研究可以做出的主要贡献是 对炎症反应的基本机制的理解。 这些研究可以导致设计减少影响的治疗方法 治疗慢性炎症，提高组织恢复率 损坏。

Serum amyloid A (SAA) is associated with reactive amyloidosis that occurs as a consequence of chronic infection and inflammatory diseases such as rheumatoid arthritis, granulomatous bowel disease or osteomyelitis. It is also associated with Familial Mediterranean Fever (FMF) and occasionally in asymptomatic individuals with FMF kindreds. In reactive amyloidosis, deposition of amyloid fibrils composed of protein AA, a degradative product of the polymorphic serum amyloid A protein, can occur in multiple organs resulting in their dysfunction. Although the etiology or pathogenic mechanisms of this process is incompletely understood, increased biosynthesis of the involved protein, SAA, under chronic inflammatory condition is quite evident. A cascade of molecular events involving cytokines released during the inflammatory processes like chronic infection and rheumatoid arthritis, trigger the overexpression of SAA, the precursor of amyloid fibrils found in tissues affected by secondary or reactive amyloidosis.. Understanding the activation mechanism of the dysregulated SAA expression may provide useful information on the pathogenesis of the SAA-linked disease. It is hypothesized that increased expression of SAA gene induced by the factors activated during chronic inflammation is a major molecular event that triggers the observed pathogenic condition. To elucidate the molecular events responsible for the overexpression of SAA in chronic inflammatory condition, we intend to pursue the following objectives: 1) characterization of SIF, a novel cytokine-inducible inflammatory factor, 2) role of different inflammatory cytokines on SAA expression in extra-hepatic cells 3) expression pattern of SIF under acute and chronic conditions, 4) interaction of the IL-1 induced nuclear factor with SIF, and 5) structural analysis of SIF. Identification and characterization of cellular factors and their interaction with cis-acting elements of SAA gene will be studied by the gel mobility shift assay, competition analyses, use of inhibitors, cotransfection analysis and site- directed mutagenesis. The major contribution that this study can make is an understanding of the basic mechanisms of response to inflammation. These studies can lead to the design of treatments to reduce the effects of chronic inflammation and increase the rate of recovery from tissue damage.