Effects of oxidative stress during ischemia-reperfusion on cytokine production in monocytes and lymphocytes

缺血再灌注过程中氧化应激对单核细胞和淋巴细胞细胞因子产生的影响

• 批准号: 14370486
• 负责人: ARAI Toshiyuki
• 金额: $ 9.02万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14370486/
• 关键词: monocytes; lymphocytes; T cells; oxidative stress; 6-formylpterin; cell death; immune responses; NF-κB; サイトカイン産生; 細胞増殖; レポーターアッセイ; 過酸化水素; 9-ホルミルプテリン; フローサイトメトリー

To elucidate the effects of oxidative stress during ischemia-reperfusion on cytokine production in monocytes and lymphocytes, the follwing studies were performed using flow cytometry and biochemical assay.1) Effects of hydrogen peroxide as an external oxidative stress and 6-formylpterin (6FP) as an internal one on cell death were examined. The results showed that the resistance against an external and an internal oxidative stress were different between monocytes and lymphocytes.2) Effects of oxidative stress on cytokine production in monocytes were examined. The results showed that neither external nor internal oxidative stress affected the cytokine production in monocytes.3) Effects of 6FP on cytokine production and cell proliferation in T cells were examined. The results showed that both of the cytokine production and the cell proliferation were suppressed by 6FP.4) Effects of 6FP on NF-κB activation in T cells were examined. The results showed that 6FP did not affect the translocation of NF-κB but inhibited the NF-κB-dependent transcription.In conclusion, it was revealed that oxidative stress did not affect the inflammatory responses of monocytes but that oxidative stress suppressed the immune response of T cells by the inhibition of the NF-κB-dependent transcription.

为了阐明缺血再灌注过程中氧化应激对单核细胞和淋巴细胞细胞因子产生的影响，我们采用流式细胞术和生化实验进行了以下研究。1)研究了过氧化氢作为外部氧化应激和6-甲酰基蝶呤（6FP）作为内部氧化应激对细胞死亡的影响。结果表明，单核细胞和淋巴细胞对外部和内部氧化应激的抵抗能力存在差异。2)观察氧化应激对单核细胞细胞因子产生的影响。结果表明，外部和内部氧化应激均不影响单核细胞细胞因子的产生。3)检测6FP对T细胞细胞因子产生和细胞增殖的影响。结果表明，6FP抑制了细胞因子的产生和细胞的增殖。4)观察6FP对T细胞NF-κB活化的影响。结果表明，6FP不影响NF-κB的易位，但抑制NF-κB依赖性转录。综上所述，氧化应激不影响单核细胞的炎症反应，但通过抑制NF-κ b依赖性转录抑制T细胞的免疫反应。

项目成果

Nishioka M, Arai T, Yamashita K, Sasada M, Mori H, Ishii H, Tajima K, Makino K, Fukuda K: "Effects of 6-formylpterin as an internal source of hydrogen peroxide on cell death of human peripheral blood leukocytes."Life Sci. 73. 221-231 (2003)

Nishioka M、Arai T、Yamashita K、Sasada M、Mori H、Ishii H、Tajima K、Makino K、Fukuda K：“6-甲酰蝶呤作为过氧化氢内部来源对人外周血白细胞细胞死亡的影响。”

Maiko Nishioka, Toshiyuki Arai, et al.: "Effects of 6-formylpterin as an internal source of hydrogen peroxide on cell death of human peripheral blood leukocytes"Life Sciences. (in press). (2003)

Maiko Nishioka、Toshiyuki Arai 等人：“6-甲酰蝶呤作为过氧化氢内部来源对人外周血白细胞细胞死亡的影响”生命科学。

Arai T, et al.: "Effects of intracellular reactive oxygen species generated by 6-formylpterin on T cell functions"Biochemical Pharamacology. 67. 1185-1193 (2004)

Arai T 等人：“6-甲酰蝶呤产生的细胞内活性氧对 T 细胞功能的影响”生化药理学。

Funakoshi T, Miyata H, Imoto T, Arai T, et al.: "6-1formylpterin protects retinal neurons from transient ischemia-reperfusion injury in rats a morphorogical and immunohistochemical study"Neuropathology. 23. 161-168 (2003)

Funakoshi T、Miyata H、Imoto T、Arai T 等人：“一项形态学和免疫组织化学研究，6-1 甲酰蝶呤可保护大鼠视网膜神经元免受短暂性缺血再灌注损伤”神经病理学。

Funakoshi T, Miyata H, Imoto T, Arai T, et al.: "6-Formylpterin protects retinal neurons from transient ischemia-reperfusion injury in rats : a morphological and immunohistochemical study"Neuropathology. 23. 161-168 (2003)

Funakoshi T、Miyata H、Imoto T、Arai T 等人：“6-甲酰蝶呤保护大鼠视网膜神经元免受短暂性缺血再灌注损伤：形态学和免疫组织化学研究”神经病理学。