A ROLE OF CYTOKINE IN PROGRESSION OF HEART FAILRE

细胞因子在心力衰竭进展中的作用

• 批准号: 07670750
• 负责人: YAMAGUCHI Seiji
• 金额: $ 1.41万
• 依托单位: Yamagata University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07670750/
• 关键词: CONGESTIVE HEART FAILURE; TUMOR NECROSIS FACTOR (TNF); SOLUBLE TNF RECEPTORS; CYTOKINE; soluble TNF receoptr; heart frilure; Interleukir 10; 腫瘍壊死因子; レセプター; 心不全; 液性因子

TNFalpha exerts its functions by binding to two specific receptors (TNF-RI and TNF-RII). The extracellular domains of TNF-RI and-RII are proteolytically cleaved (sTNF-RI and sTNF-RII) and neutralize the effects of TNF alpha. We investigated the surface and gene expressions of TNF-RII and the shedding of TNF-RII on mononulear leukocytes in patients with congestive heart failure (CHF). Mononuclear leukocytes were separated from peripheral blood in 14 control and in 21 patients with CHF.The surface expression of TNF-RII by immunofluorescence flow cytometry was increased in relation to the severity of CHF (NYHA class). TNF-RII mRNA level by Northern blot analysis was relatively higher in patients with advanced CHF.To assess the feasibility of shedding TNF-RII in ^ハmononuclear leukocytes, the cells from patients with CHF and control subjects were incubated in the absence and presence of phorbol myristate acetate (PMA). sTNF-RII in the supernatant with PMA was higher in CHF than control (p<.05). Furthermore, shedding of TNF-RII was higher in the supernatant of mononuclear leukocyts of volunteers treated with 10% serum from CHF than those from control (p<.05). In conclusion, TNF-RII on mononuclear leukocytes was up-regulated in patients with CHF.In addition to feasibility of shedding of TNF-RII on mononuclear leukocytes in CHF,serum from patients with CHF enhanced shedding of TNF-RII on the cells. The presence of CHF affects TNF alpha-TNF receptor system which may modify systemic manifestations including alteration of immune system in CHF.

TNFα 通过与两种特定受体（TNF-RI 和 TNF-RII）结合发挥其功能。TNF-RI 和 TNF-RII 的胞外结构域被蛋白水解裂解（sTNF-RI 和 sTNF-RII）并中和 TNF α 的作用。我们研究了充血性心力衰竭患者单核白细胞上 TNF-RII 的表面和基因表达以及 TNF-RII 的脱落(CHF) 从 14 名对照者和 21 名 CHF 患者的外周血中分离出单核白细胞。免疫荧光流式细胞术显示 TNF-RII 的表面表达与 CHF 的严重程度相关（NYHA 级别）。 Northern blot分析表明，晚期CHF患者的TNF-RII水平相对较高。为了评估单核白细胞中脱落TNF-RII的可行性，CHF患者和对照细胞的细胞受试者在不存在和存在佛波醇肉豆蔻酸酯(PMA)的情况下与PMA上清液中的sTNF-RII一起培养，在CHF中比对照更高(p<.05)。此外，在CHF的上清液中TNF-RII的脱落也更高。与对照组相比，用 10% CHF 血清治疗的志愿者的单核白细胞数量有所增加 (p<.05)。 总之，TNF-RII 对单核细胞的影响。 CHF 患者的白细胞表达上调。除了 CHF 患者的单核白细胞上 TNF-RII 脱落的可能性外，CHF 患者的血清还增强细胞上 TNF-RII 的脱落。CHF 的存在影响 TNF α-TNF。受体系统可能会改变全身表现，包括 CHF 免疫系统的改变。

项目成果

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