Effects of mitochondrial dysfunction on the immunological properties of microglia.
Effects of mitochondrial dysfunction on the immunological properties of microglia.
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DOI：
10.1186/1742-2094-7-45
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发表时间：
2010-08-11
影响因子：
9.3
通讯作者：
Witting A
中科院分区：
文献类型：
--
作者：
Ferger AI;Campanelli L;Reimer V;Muth KN;Merdian I;Ludolph AC;Witting A
神经退行性疾病的特征在于线粒体功能障碍和小胶质细胞（脑的巨噬细胞）的活化。在这里，我们研究线粒体功能障碍对小胶质细胞活化的影响。我们将原代小鼠小胶质细胞与线粒体毒素3-硝基丙酸（3-NP）或鱼藤酮孵育。已知这些线粒体毒素在人类和实验动物中诱导神经变性。我们的特点是脂多糖-（LPS-）诱导的小胶质细胞活化和替代，白细胞介素-4-（IL-4-）诱导的小胶质细胞活化在这些线粒体毒素处理的小胶质细胞。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α（TNF-α），白细胞介素-6（IL-6）和白细胞介素-1 β（IL-1β）的释放所测量的，但它们确实抑制了IL-4诱导的部分交替激活，如谷胱甘肽转移酶活性和表达所测量的，胰岛素样生长因子1（IGF-1）的诱导和LPS诱导的细胞因子释放的抵消。小胶质细胞中的线粒体功能障碍抑制了IL-4诱导的部分替代反应。因为这种替代活化被认为与伤口愈合和炎症减弱相关，所以小胶质细胞中的线粒体功能障碍可能导致神经退行性疾病中观察到的神经炎症的有害影响。
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. 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. We found that, while mitochondrial toxins did not affect LPS-induced activation, as measured by release of tumor necrosis factor α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β), 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. 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.
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影响因子：
5.3
作者：
Ponomarev, Eugene D.;Maresz, Katarzyna;Dittel, Bonnie N.
通讯作者：
Dittel, Bonnie N.
DOI：
10.1016/j.bbrc.2009.11.174
发表时间：
2010-01-01
影响因子：
3.1
作者：
Kim, Tae Woo;Yim, Sujin;Park, Kyung Chan
通讯作者：
Park, Kyung Chan
影响因子：
29
作者：
Vats, Divya;Mukundan, Lata;Chawla, Ajay
通讯作者：
Chawla, Ajay
影响因子：
5.3
作者：
Gao, HM;Hong, JS;Liu, B
通讯作者：
Liu, B
影响因子：
5.3
作者：
Austin, Susan A.;Floden, Angela M.;Combs, Colin K.
通讯作者：
Combs, Colin K.