Department of Physiology, Fujita Health University School of Medicine, Toyoake, Japan.
Neurodegener Dis. 2012;10(1-4):100-3. doi: 10.1159/000332936. Epub 2012 Feb 1.
Activated microglia secrete inflammatory cytokines and may play roles in the progression of neurodegenerative diseases. However, the mechanism underlying microglial activation remains unclear.
Our aim was to examine the regulation of activated microglia through their cell death and survival pathways.
We used mouse primary-cultured microglia, which are destined to die within a few days under ordinary culture conditions. The microglia live for longer than 1 month, without any measurable increase in apoptotic or necrotic cell death, when kept activated by sublethal concentrations of lipopolysaccharide (LPS).
LPS-treated microglia showed changes in shape. LPS treatment had no effect on the level of the proapoptotic Bcl-2-associated X protein but increased the level of the antiapoptotic protein Bcl-xL at day 1. Furthermore, the level of microtubule-associated light chain 3-II, a marker protein for autophagy, was decreased 3 h after exposure to LPS.
An increase in Bcl-xL seems to inhibit both apoptosis and autophagy. Our results suggest that long-lived microglia resulting from exposure to the optimal dose of LPS may play critical roles in the progression of neurodegeneration.
激活的小胶质细胞分泌炎症细胞因子，并可能在神经退行性疾病的进展中发挥作用。然而，小胶质细胞激活的机制仍不清楚。
我们旨在通过细胞死亡和存活途径来研究激活的小胶质细胞的调节。
我们使用注定在普通培养条件下几天内死亡的原代培养的小鼠小胶质细胞。当用亚致死浓度的脂多糖（LPS）使小胶质细胞保持激活状态时，它们的存活时间超过 1 个月，凋亡或坏死性细胞死亡没有任何可测量的增加。
LPS 处理的小胶质细胞形态发生变化。LPS 处理对促凋亡 Bcl-2 相关 X 蛋白（Bcl-2-associated X protein）的水平没有影响，但在第 1 天增加了抗凋亡蛋白 Bcl-xL 的水平。此外，暴露于 LPS 3 小时后，微管相关轻链 3-II（自噬的标志物蛋白）的水平降低。
Bcl-xL 的增加似乎抑制了细胞凋亡和自噬。我们的结果表明，暴露于最佳剂量的 LPS 后产生的寿命长的小胶质细胞可能在神经退行性变的进展中发挥关键作用。
