Involvement of interleukin-1β in the mechanism of human immunodeficiency virus type 1 (HIV-1) recombinant protein gp120-induced apoptosis in the neocortex of rat
Involvement of interleukin-1β in the mechanism of human immunodeficiency virus type 1 (HIV-1) recombinant protein gp120-induced apoptosis in the neocortex of rat
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DOI：
10.1016/s0306-4522(98)00363-7
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发表时间：
1999-04-01
期刊：
影响因子：
3.3
通讯作者：
Finazzi-Agró, A
中科院分区：
文献类型：
--
作者：
Bagetta, G;Corasaniti, MT;Finazzi-Agró, A
通过免疫组织化学方法，研究了亚慢性脑室内注射人类免疫缺陷病毒 1 型 (HIV-1) 重组蛋白 gp120（100 ng，每天给药，最多连续 7 天）对成年大鼠大脑中 interieukin-1 β 表达的影响。与对照组相比，经牛血清白蛋白（300 ng，脑室内注射长达 7 天）治疗的动物 (n=6)，在分析前 24 小时接受单次注射病毒蛋白的大鼠 (n=6) 的大脑皮层和海马中白细胞介素-1 β 免疫反应性增加，并且在治疗 7 天后在大脑的这些区域 (n=6) 观察到更显着的增加。双标记免疫荧光实验支持 gp120 增强的白细胞介素 1 β 表达的神经元和可能的小胶质细胞起源。脑组织切片的透射电子显微镜分析显示，使用 gp120 (100 ng) 和白细胞介素 1 受体拮抗剂 (80 ng) 或白细胞介素转换酶抑制剂 II (100 pmol) 联合治疗（每天脑室内给药，持续 7 天），但不能与亮肽素 (100 pmol) 联合治疗，可防止通常由病毒蛋白引起的大鼠（n=6/组）脑皮质细胞的凋亡性死亡。这些数据表明gp120增强大脑中白细胞介素-1p的表达，这可能涉及gp120诱导大鼠大脑皮层细胞凋亡的机制。这一假设的进一步支持来自以下证据：脑室内注射鼠重组白细胞介素 1 β（200 U，连续 7 天每天注射）会在大鼠 (n=6) 的大脑皮层中产生 DNA 碎片。有趣的是，后一种治疗增强了海马体中的神经生长因子水平，而不是大脑皮层中的神经生长因子水平，这与最近报道的用 gp120 进行同样治疗的大鼠相同大脑区域中的类似效果相一致。 总之，目前的数据表明，用 gp120 治疗增强了白细胞介素 1 β 的表达，这参与了大鼠大脑皮层中细胞凋亡的机制。相比之下，在海马体中，gp120 增强的白细胞介素 1 β 表达会提高神经生长因子的水平，从而可能阻止或延迟大鼠大脑可塑性区域的细胞凋亡。 (C) 1999 国际广播组织。由爱思唯尔科学有限公司出版
The effect of subchronic intracerebroventricular injection of the human immunodeficiency virus type 1 (HIV-1) recombinant protein gp120 (100 ng, given daily for up to seven consecutive days) on interieukin-1 beta expression was studied by immunohistochemistry in the brain of adult rats. In comparison to control, bovine serum albumin (300 ng, given intracerebroventricularly for up to seven days) -treated animals (n=6), interreukin-1 beta immunoreactivity increased in the brain cortex and hippocampus of rats (n=6) receiving a single injection of the viral protein 24 h before analysis with more substantial increases being observed in these regions of the brain (n=6) after seven days treatment. Double-labelling immunofluorescence experiments support a neuronal and, possibly, a microglial cell origin for gp120-enhanced interleukin-1 beta expression. Transmission electron microscopy analysis of brain tissue sections revealed that combination treatments (given intracerebroventricularly daily for seven days) with gp120 (100 ng) and interleukin-1 receptor antagonist (80 ng) or with the interleukin converting enzyme inhibitor II (100 pmol), but not with leupeptin (100 pmol), prevented apoptotic death of rat (n=6/group) brain cortical cells typically elicited by the viral protein. These data demonstrate that gp120 enhances interleukin-lp expression in the brain and this may be involved in the mechanism underlying apoptosis induced by gp120 in the brain cortex of rat. Further support to this hypothesis comes from the evidence that intracerebroventricular injection of murine recombinant interleukin-1 beta (200 U, given daily for seven consecutive days) produces DNA fragmentation in the brain cortex of rat (n=6). Interestingly, the latter treatment enhanced nerve growth factor level in the hippocampus but not in the cerebral cortex and this coincides with a similar effect recently reported in identical brain areas of rats treated likewise with gp120.In conclusion, the present data demonstrate that treatment with gp120 enhances interleukin-1 beta expression and this participates in the mechanism of apoptotic cell death in the brain cortex of rat. By contrast, in the hippocampus, gp120-enhanced interreukin-1 beta expression elevates nerve growth factor that may prevent or delay apoptosis in this plastic region of the rat brain. (C) 1999 IBRO. Published by Elsevier Science Ltd.