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， 由于慢性感染和炎性疾病， 类风湿性关节炎、肉芽肿性肠病或骨髓炎。是 也与家族性地中海热（FMF）有关，偶尔 FMF激酶的无症状个体。在反应性淀粉样变性中， 由蛋白质AA组成的淀粉样纤维的沉积， 多态性血清淀粉样蛋白A蛋白的产物，可以发生在多个 导致其功能障碍。虽然病因或致病性 这一过程的机制尚未完全理解，增加了 在慢性炎症条件下， 条件很明显。一系列分子事件， 炎症过程中释放的细胞因子，如慢性炎症， 感染和类风湿性关节炎，触发SAA的过度表达， 淀粉样原纤维的前体，发现于继发性或 反应性淀粉样变性了解的激活机制 SAA表达失调可能提供有用的信息， SAA相关疾病的发病机制。据推测， 慢性胰腺炎时激活因子诱导SAA基因表达 炎症是一个主要的分子事件，触发观察到的 致病状态 为了阐明负责过度表达的分子事件， SAA在慢性炎症条件下，我们打算追求以下 目的：1）SIF，一种新的尼古丁诱导的 炎性因子，2）不同炎性细胞因子对SAA的作用 3）急性肝损伤后SIF的表达模式 4）IL-1诱导的核因子相互作用 5）SIF的结构分析。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变动分析来研究， 竞争分析、抑制剂的使用、共转染分析和位点- 定向诱变这项研究的主要贡献是 了解炎症反应的基本机制。 这些研究可能会导致治疗设计，以减少影响 慢性炎症和增加从组织的恢复率 损害

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.