线粒体功能障碍对小胶质细胞免疫特性的影响。

BACKGROUND

Neurodegenerative diseases are characterized by both mitochondrial dysfunction and activation of microglia, the macrophages of the brain. Here, we investigate the effects of mitochondrial dysfunction on the activation profile of microglial cells.

METHODS

We incubated primary mouse microglia with the mitochondrial toxins 3-nitropropionic acid (3-NP) or rotenone. These mitochondrial toxins are known to induce neurodegeneration in humans and in experimental animals. We characterized lipopolysaccharide- (LPS-) induced microglial activation and the alternative, interleukin-4- (IL-4-) induced microglial activation in these mitochondrial toxin-treated microglial cells.

RESULTS

We found that, while mitochondrial toxins did not affect LPS-induced activation, as measured by release of tumor necrosis factor alpha (TNF-alpha), interleukin-6 (IL-6) and interleukin-1beta (IL-1beta), they did inhibit part of the IL-4-induced alternative activation, as measured by arginase activity and expression, induction of insulin-like growth factor 1 (IGF-1) and the counteraction of the LPS induced cytokine release.

CONCLUSIONS

Mitochondrial dysfunction in microglial cells inhibits part of the IL-4-induced alternative response. Because this alternative activation is considered to be associated with wound healing and an attenuation of inflammation, mitochondrial dysfunction in microglial cells might contribute to the detrimental effects of neuroinflammation seen in neurodegenerative diseases.

背景

神经退行性疾病的特点是线粒体功能障碍和小胶质细胞（大脑中的巨噬细胞）的激活。在这里，我们研究了线粒体功能障碍对小胶质细胞激活谱的影响。

方法

我们用线粒体毒素 3-硝基丙酸（3-NP）或鱼藤酮孵育原代小鼠小胶质细胞。这些线粒体毒素已知可诱导人类和实验动物的神经退行性变。我们在这些线粒体毒素处理的小胶质细胞中表征了脂多糖（LPS）诱导的小胶质细胞激活和替代的白细胞介素 4（IL-4）诱导的小胶质细胞激活。

结果

我们发现，虽然线粒体毒素不影响 LPS 诱导的激活，如肿瘤坏死因子 alpha（TNF-alpha）、白细胞介素 6（IL-6）和白细胞介素 1beta（IL-1beta）的释放所测量的，它们确实抑制了部分 IL-4 诱导的替代激活，如精氨酸酶活性和表达、胰岛素样生长因子 1（IGF-1）的诱导以及 LPS 诱导的细胞因子释放的拮抗作用。