The role of chemokine in human nephritis and basic research of anti-chemokine therapy in experimental nephritis model.

趋化因子在人肾炎中的作用及实验性肾炎模型抗趋化因子治疗的基础研究。

• 批准号: 09671157
• 负责人: YOKOYAMA Hitoshi
• 金额: $ 1.92万
• 依托单位: Kanazawa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09671157/
• 关键词: Glomerulonephritis; IgA nephropathy; Experimental nephritis; Chemokine; IL-8; MCAF; MCP-1; Adhesion molecule; Soluble form of adhesion molecule; Eotaxin; ループス腎炎; p-セレクチン; ICAM-1

We investigated the pathophysiological roles of a potent macrophage (Mphi) chemokine, monocyte chemotactic and activating factor (MCAF/MCP-1), in a crescentic glomerulonephritis model of Wistar-Kyoto rats. Anti-MCAF/MCP-1 antibodies decreased proteinuria on day 3 and 6, and also decreased the number of Mphi in glomeruli and crescentic formation in nephritic rats. Furthermore, anti-M CAF/MCP- 1 antibodies remarkably reduced glomerulosclerosis and improved renal dysfunction on day 56. The single administration of anti-MCAF/MCP- I antibodies on day 7 decreased necrotizing lesions and increase of proteinuria as compared with control lgG treated rats. These results suggest that MCAF/MCP-1 essentially participates in the impairment of renal functions associated with crescentic glomerulonephritis by both recruitin2 and activating Mphi in the early phase. We also investigated the involvement of chemokines and the expression of adhesion molecules in human nephritis. Urinary and serum MCAF/MCP-1 levels were significantly high in patients with lupus nephritis including WHO lVb/c. in addition, MCAF and IL-S were differentially expressed in kidneys with IgA nephropathy, and their subtypes. P-selectin and IL-8 were expressed in glomeruli of proliferative glomerulonephritis and were correlated with endocapillary proliferation, CD4Ib (activated platelets) and leukocyte infiltration.

我们在Wistar-kyoto大鼠的新月形肾小球肾炎模型中研究了有效巨噬细胞（MPHI）趋化因子，单核细胞趋化因子和激活因子（MCAF/MCP-1）的病理生理作用。抗MCAF/MCP-1抗体在第3和第6天降低了蛋白尿，也减少了肾小球大鼠肾小球和新月形形成的MPHI数量。此外，抗M CAF/MCP-1抗体明显降低了肾小球硬化症并改善了第56天的肾功能障碍。与对照LGG治疗的老鼠相比，第7天的抗MCAF/MCP- I抗体单一施用抗MCP- I抗体降低了坏死性病变，并增加了蛋白尿。这些结果表明，MCAF/MCP-1基本上参与了肌肉肾小球肾上腺炎和肌肉肾小球肾炎相关的肾功能损害，并在早期阶段激活MPHI。我们还研究了趋化因子的参与和粘附分子在人肾炎中的表达。狼疮性肾炎患者（包括LVB/c）患者的尿和血清MCAF/MCP-1水平显着高。此外，在患有IGA肾病及其亚型的肾脏中，MCAF和IL-S在肾脏中差异表达。 P-选择素和IL-8在增殖性肾小球肾炎的肾小球中表达，并与内毛毛细血管增殖，CD4IB（活化血小板）和白细胞浸润相关。

项目成果

Hitoshi Yokoyama et al.: "Glomerular ICAM-1 Expression related to circulating TNF-alpha in human glomerulonephritis." Nephron. 76. 425-433 (1997)

Hitoshi Yokoyama 等人：“肾小球 ICAM-1 表达与人肾小球肾炎中循环 TNF-α 相关。”

Hitoshi Yokoyama: "Urinary levels of chemokines (MCAF/MCP-1,IL-8) reflect distinct disease activities and phases of human IgA nephropathy." J Leuk Biol. 63. 493-499 (1998)

Hitoshi Yokoyama：“趋化因子（MCAF/MCP-1、IL-8）的尿液水平反映了人类 IgA 肾病的不同疾病活动和阶段。”

Chikako Segawa: "In situ expression and soluble from of P-selektin in human glomerulonephritis." Kindney international. 52. 1054-1063 (1997)

Chikako Sekawa：“P-selektin 在人肾小球肾炎中的原位表达和可溶性。”

Hitoshi Yokoyama et al.: "Urinary levels of chemokines (MCAF/MCP-1, IL-8) reflect distinct disease activities and phases of human IgA nephropathy." J Leuk Biol. 63. 493-499 (1998)

Hitoshi Yokoyama 等人：“趋化因子（MCAF/MCP-1、IL-8）的尿液水平反映了人类 IgA 肾病的不同疾病活动和阶段。”