Investigation for the pathogenesis of secondary amyloidosis complicated with rheumatoid arthritis

继发性淀粉样变性并发类风湿性关节炎发病机制探讨

• 批准号: 11670452
• 负责人: MIGITA Kiyoshi
• 金额: $ 1.79万
• 依托单位: Nagasaki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11670452/
• 关键词: Serum amyloid A protein; β2-microglobulin; amyloidosis; cyclooxygenase-2; cytokine; Rhumatoid arthritis; IL-18; 単球; シクロオキシゲナーゼ

#1 Induction of COX-2 by β2-microglobulinβ2-microglobulin treatment increased the induction of COX-2 mRNA and COX-2 protein synthesis from human rheumatoid synovial cells in a dose-dependent manner. Dexamethasone suppressed the induction of COX-2 mRNA and protein in β2-microglobulin-stimulated synovial cells. These data indicated that COX-2 expression by β2-micoglobulin may be an important inflammatory process in hemodialysis associated osteoaithropathy.#2 Impaired degradation of serum amyloid A protein by cytokine-stimulated monocytes.CD14+ monocytes degraded SAA completely in vitro. When CD14* monocytes were pretreated with IL-1 β or IFN-γ, increasing amounts of SAA-related derivatives were detected in culture supernatants. This down-regulated proteolysis of SAA protein by cytokine stimulated monocytes may play a role in the mechanism of impaired SAA metabolism.

#1 β 2-微球蛋白对考克斯-2的诱导β 2-微球蛋白处理以剂量依赖性方式增加了人类风湿性滑膜细胞对考克斯-2 mRNA和考克斯-2蛋白合成的诱导。地塞米松抑制β2-微球蛋白刺激滑膜细胞诱导考克斯-2 mRNA和蛋白表达。这些数据表明，β2-微管蛋白表达考克斯-2可能是血液透析相关性骨关节病的重要炎症过程。2.CD14+单核细胞在体外可完全降解SAA。当用IL-1 β或IFN-γ预处理CD 14 * 单核细胞时，在培养上清液中检测到数量增加的SAA相关衍生物。细胞因子刺激的单核细胞下调SAA蛋白的蛋白水解可能在SAA代谢受损的机制中发挥作用。

项目成果

Kiyoshi Migita: "Impaired degradation of serum amyloid A(SAA) protein by cytokine-stimulated monocytes"Clin Exp Immunol. 123(3). 408-411 (2001)

Kiyoshi Migita：“细胞因子刺激的单核细胞对血清淀粉样蛋白 A (SAA) 蛋白的降解受损”Clin Exp Immunol。

Migita K,et al: "Regulation of rheumatoid synovial cell growth by ceramide"Biochem Biophy Res Commun in press. (2000)

Migita K 等人：“神经酰胺调节类风湿滑膜细胞生长”Biochem Biophy Res Commun 正在出版。

K.Migita. et al: "Impaired degradation of serum amyloid A (SAA) protein by cytokine-stimulated monocytes by cytokine-stimulated monocytes"Clinical and Experimental Immunology. (in press). (2001)

K.米吉塔.