Differential effects of interleukin-1 beta and S100B on amyloid precursor protein in rat retinal neurons

被引：0

作者：

Anderson, Peter J. B. ^{[1
]}

Watts, Helena R. ^{[1
]}

Jen, Sheila ^{[1
]}

Gentleman, Stephen M. ^{[2
]}

Moncaster, Juliet A. ^{[1
]}

Walsh, D. T. ^{[1
]}

Jen, Ling-Sun ^{[1
]}

机构：

[1] Imperial Coll London, Hammersmith Hosp, Div Neurosci & Mental Hlth, Dept Cellular & Mol Neurosci, Burlington Danes Bldg,160 Du Cane Rd, London W12 0NN, England

[2] Imperial Coll London, Hammersmith Hosp, Div Neurosci & Mental Hlth, Dept Clin Neurosci, London, England

来源：

CLINICAL OPHTHALMOLOGY | 2009年 / 3卷

基金：

美国国家卫生研究院;

关键词：

Alzheimer's disease; interleukin; 1; beta; S100B; amyloid precursor protein; amyloid-beta; retina;

D O I：

暂无

中图分类号：

R77 [眼科学];

学科分类号：

100212 ;

摘要：

Purpose: Interleukin-1 beta (IL-1 beta) and S100B calcium binding protein B (S100B) have been implicated in the pathogenesis of Alzheimer's disease. Both are present in and around senile plaques and have been shown to increase levels of amyloid precursor protein (APP) mRNA in vitro. However, it is not known how either of these substances affects APP in vivo. Methods: We have studied the effects of IL-1 beta and S100B on the expression and processing of APP using a retinal-vitreal model. We have also investigated the effect of amyloid beta peptide (A beta) on APP in the same system and the regulation of S100B production by A beta and IL-1 beta from retinal glial cells. Results: Retinal ganglion cells constitutively express APP. However, after intravitreal injection of IL-1 beta or A beta there was a marked reduction in APP levels as detected by Western blotting and IL-1 beta produced a decrease in APP immunoreactivity (IR). Nissl staining showed that the integrity of the injected retinas was unchanged after injection. Two days after S100B injection, there was a small reduction in APP-IR but this was accompanied by the appearance of some intensely stained large ganglion cells and there was some up-regulation in APP holoprotein levels on Western blot. Seven days post-S100. injection, these large, highly stained cells had increased in number throughout the retina. Injection of A beta and IL-1 beta also caused an increase in S100B production within the retinal Muller glial cells. Conclusion: These results support the hypothesis that S100B (a glial-derived neurotrophic factor) and IL-1 beta (a pro-infl ammatory cytokine) can modulate the expression and processing of APP in vivo and so may contribute to the progression of Alzheimer's disease.

引用

页码：235 / 242

页数：8