Relations between development of insulitis and expression of adhesion molecules in multiple low-dose streptozotocin-treated mice.

多只低剂量链脲佐菌素治疗的小鼠中胰岛素炎的发生与粘附分子表达之间的关系。

• 批准号: 06660381
• 负责人: HAYASHI Toshiharu
• 金额: $ 1.28万
• 依托单位: Yamaguchi University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06660381/
• 关键词: Insulitis; IDDM; ICAM-I; LFA-I; type 2 reovirus; Autoimmune disease; Streptozotocin; SLE; LDV; 血管内皮細胞

Summary consisted of five papers listed bellow.Multiple low-dose streptozotocin (SZ) -induced insulitis is an animal model for human insulin-dependent diabetes mellitus (IDDM) characterized by a mononuclear cell infiltration. SZ-induced insulitis and blood glucose concentrations were reduced by treatment with anti-ICAM-1 and anti-LFA-1 monoclonal antibodies (Ref.1). ICAM-1 expression on vascular endothelial cells increased in parallel to the degree of insulitis. Also NZBxNZWF1 mice, which is an animal model for human systemic lupus erythematosus, showed increased accumulation of neutrophils, macrophages, T and CD4 <plus-minus> cells expressing LFA-1 molecule within glomeruli during the development of glomerulonephritis (GN). The NZBxNZWF1 mice exhibited an age-related and profound increase in ICAM-1 expression associated with the development of GN (Ref.3). In LDV infected mice, suppressed expression of these molecules was related with the suppression of insulitis or GN (Ref.1-3). This suppressive effect in LDV-infected mice may not be due to altered IL-6 production by macrophages (Ref.4). On the other hand, reovirus type 2-induced diabetes-like syndrome in suckling DBA/1 mice is considered to be another animal model for human IDDM.The treatment with monoclonal antibodies against ICAM-1 and LFA-1 prevented the development of insulitis with abnormal glucose tolerance (Ref.5). In conclusion, our observations indicate a potential therapeutic application of these antibodies in certain autoimmune disease

摘要由以下五篇论文组成。多重低剂量链脲佐菌素（SZ）诱导的胰岛素依赖性糖尿病（IDDM）是一种以单核细胞浸润为特征的动物模型。用抗icam -1和抗lfa -1单克隆抗体治疗可降低sz诱导的胰岛素和血糖浓度（参考文献1）。ICAM-1在血管内皮细胞上的表达随胰岛素炎症程度的增加而增加。此外，作为人系统性红斑狼疮动物模型的NZBxNZWF1小鼠在肾小球肾炎（glomerulonephritis， GN）的发展过程中，肾小球内中性粒细胞、巨噬细胞、T细胞和表达LFA-1分子的CD4 <正负>细胞的积累增加。NZBxNZWF1小鼠表现出与GN发展相关的ICAM-1表达的年龄相关性和深度增加（参考文献3）。在LDV感染小鼠中，这些分子的抑制表达与胰岛素或GN的抑制有关（参考文献1-3）。在ldv感染的小鼠中，这种抑制作用可能不是由于巨噬细胞改变了IL-6的产生（参考文献4）。另一方面，呼肠孤病毒2型诱导的哺乳期DBA/1小鼠的糖尿病样综合征被认为是人类IDDM的另一动物模型。用抗ICAM-1和LFA-1的单克隆抗体治疗可阻止糖耐量异常的胰岛素炎的发展（参考文献5）。总之，我们的观察表明这些抗体在某些自身免疫性疾病中具有潜在的治疗应用

项目成果

T.Hayashi: "Effect of infection by LDV on expression of ICAM-1 on vascular endothelial cells of pancreatic islets in SZ-incluced insulitis of CD-1 mice" Int.J.Exp.Path.75. 211-217 (1994)

T.Hayashi：“LDV 感染对 CD-1 小鼠 SZ 性胰岛炎中胰岛血管内皮细胞 ICAM-1 表达的影响”Int.J.Exp.Path.75。

4. IWATA. H. AND HAYASHI. T.: "Interleukin-6 production by macrophages from BALB/c mice with a chronic infection of lactic dehydrogenase virus." Exp. Anim.43,. 559-562. (1994)

4.岩田。

1. HAYASHI. T., HASHIMOTO. S., AND KAMEYAMA Y.: "Reduced steptozotocin-induced insulitis in Cl)-I mice by treament with anti-intracellular adhesion molecule-l and anti-lymphocyte function associated antigen-1 monoclonal antibosies together with lactic deh

1.林。

Iwata, H.and Hayashi, T.: "Interleukin-6 production by macrophages from BALB/c mice with a chronic infection of lactic dehydrogenase virus." Exp.Anim.43. 559-562 (1994)

Iwata, H. 和 Hayashi, T.：“慢性感染乳酸脱氢酶病毒的 BALB/c 小鼠巨噬细胞产生白介素 6。”

2. HAYASHI. T., HASHIMOTO. S., AND KAWASHIMA. A.: "Effect of infection by lactic dehydrogenase virus on expression of intercelluar adhesion molecule-1 on vascular endothelial cells of pancreatic islets in stretozotocin-induced insulitis of CD-1 mice." Int

2.林。