A mechanism of HIV-related dementia complex - relation between TNF-α and dementia -

HIV相关痴呆症复合体的机制 - TNF-α与痴呆症之间的关系 -

• 批准号: 13680840
• 负责人: SAITO Kuniaki
• 金额: $ 2.24万
• 依托单位: Gifu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13680840/
• 关键词: AIDS; dementia; TNF-α; indoleamine-2, 3-dioxygenase; NO synthase; inflammatory neurological disorders; 脳神経疾患; トキソプラズマ

Role of tumor necrosis factor (TNF-alpha) in LP-BM5 murine leukemia retrovirus mixture induced neurotoxicity were investigated using TNF-alpha gene deficient (TNF-alpha -/-) mice and chimeric mice that are TNF-alpha gene deficient only in bone marrow-derived cells. Further, neurotoxic effects were tested using mouse primary neuronal cultures.Neurotoxicity was observed in media from human monocyte-derived macrophages infected with HIV-1 and activated with lipopolysaccharide were neurotoxic. These neurotoxicity was blocked by TNF-a antibody and MK801.Taken together, our results support a role for TNF-alpha in the neurodegenerative processes associated with viral infections such as HIV-1.

用肿瘤坏死因子（TNF-α）基因缺陷（TNF-α-/-）小鼠和仅在骨髓源性细胞中TNF-α基因缺陷的嵌合小鼠研究了TNF-α在LP-BM 5小鼠白血病逆转录病毒混合物诱导的神经毒性中的作用。此外，使用小鼠原代神经元培养物测试神经毒性作用，在感染HIV-1并用脂多糖激活的人单核细胞衍生的巨噬细胞的培养基中观察到神经毒性。这些神经毒性被TNF-α抗体和MK 801阻断。总之，我们的结果支持TNF-α在与病毒感染如HIV-1相关的神经退行性过程中的作用。

项目成果

Iwasaki M, et al.: "Tumor necrosis factor-α from bone marrow-derived cells is not essential for the expression of adhesion molecules in lipopolysaccaride-induced nasal inflammation"Cytokine. 21. 129-136 (2003)

Iwasaki M 等人：“来自骨髓来源的细胞的肿瘤坏死因子-α 对于脂多糖诱导的鼻炎症中粘附分子的表达不是必需的”Cytokine 21. 129-136 (2003)。

Fujigaki S, Saito K, Sekikawa K, Tone S, Takikawa O, Fujii H, Wada H, Noma A, Seishima M: "Lipopolysaccaride induction of indoleamine-2,3-dioxygenase is mediated dominantly by an TNF-α-independent mechanism"Eur J Immunol. 31. 2313-2318 (2001)

Fujigaki S、Saito K、Sekikawa K、Tone S、Takikawa O、Fujii H、Wada H、Noma A、Seishima M：“吲哚胺-2,3-双加氧酶的脂多糖诱导主要由 TNF-α 独立机制介导”欧洲免疫学杂志 31. 2313-2318 (2001)

斉藤邦明他: "生活習贋病と炎症性サイトカイン-TNF-αを中心として-"健康創造研究. 1・1. 22-29 (2002)

Kuniaki Saito 等：“生活方式相关疾病和炎症细胞因子 - 聚焦 TNF-α”健康创造研究 1・1（2002 年）。

関川賢二他: "感染症の宿主防御機構-理論と実際-腫瘍壊死因子(TNF-α)"医薬ジャーナル社. (2002)

Kenji Sekikawa 等：“针对传染病的宿主防御机制 - 理论与实践 - 肿瘤坏死因子 (TNF-α)” Iyaku Journal Co., Ltd. (2002)

Maekawa N., et al.: "Improved myocardial ischemia/reperfusion injury in mice lacking tumor necrosis factor-α"J. Am. Coll. Cardiol.. 39. 1229-1235 (2002)

Maekawa N. 等人：“改善缺乏肿瘤坏死因子-α 的小鼠的心肌缺血/再灌注损伤”J. Am. Cardiol.. 39. 1229-1235 (2002)