Vasilakos J P, Carroll R T, Emmerling M R, Doyle P D, Davis R E, Kim K S, Shivers B D
Parke-Davis Pharmaceutical Research, Division of Warner-Lambert Co., Ann Arbor, MI 48105.
FEBS Lett. 1994 Nov 14;354(3):289-92. doi: 10.1016/0014-5793(94)01142-7.
A heightened production of interleukin 1 beta (IL-1 beta) has been reported in microglial-associated amyloid deposits in Alzheimer's disease (AD) brains. These plaques are composed predominantly of beta/A4 peptide derived from beta-amyloid precursor protein (beta APP). We demonstrate that short-term (1 h) IL-1 beta-treatment increases beta APPs secretion and concomitantly decreases cell-associated beta APP in human H4 neuroglioma cells. Long-term (5 h) IL-1 beta treatment did not alter secreted or cell-associated beta APP content. In contrast, the secretion of beta/A4-containing epitope was not affected by short-term IL-1 beta stimulation; however, long-term IL-1 beta treatment decreased the amount of beta/A4-containing epitope secreted from the cells. These results show that IL-1 beta modifies the processing and secretion of beta APP to exacerbate perhaps the neuropathology of AD.
据报道，在阿尔茨海默病（AD）大脑中与小胶质细胞相关的淀粉样沉积物中，白细胞介素1β（IL-1β）的产生增加。这些斑块主要由源自β-淀粉样前体蛋白（βAPP）的β/A4肽组成。我们证明，短期（1小时）IL-1β处理可增加人H4神经胶质瘤细胞中βAPPs的分泌，并同时减少细胞相关的βAPP。长期（5小时）IL-1β处理不会改变分泌的或细胞相关的βAPP含量。相反，含β/A4表位的分泌不受短期IL-1β刺激的影响；然而，长期IL-1β处理会减少细胞分泌的含β/A4表位的量。这些结果表明，IL-1β可改变βAPP的加工和分泌，可能会加剧AD的神经病理学变化。
