Chao C C, Molitor T W, Hu S
Neuroimmunobiology and Host Defense Laboratory, Minneapolis Medical Research Foundation, MN 55404.
J Immunol. 1993 Aug 1;151(3):1473-81.
Microglia have been proposed to play a pathogenetic role in immunologically mediated neurodegenerative diseases. In our study, using microglial/neuronal cell cocultures primed with IFN-gamma, we found that both LPS and TNF-alpha triggered neuronal cell injury (impairment of gamma-aminobutyric acid uptake and neuronal loss) via a nitric oxide mechanism. Pretreatment of cell cocultures with IL-4, an immunosuppressive cytokine, prevented, in a dose-dependent manner, neuronal cell injury induced by activated microglia. The mechanism by which IL-4 exerts its neuroprotective effect was found to involve the inhibition of IFN-gamma priming of microglia with a subsequent decrease in the production of TNF-alpha and nitric oxide.
小胶质细胞被认为在免疫介导的神经退行性疾病中发挥致病作用。在我们的研究中，使用经γ干扰素预处理的小胶质细胞/神经元细胞共培养体系，我们发现脂多糖（LPS）和肿瘤坏死因子-α（TNF-α）均通过一氧化氮机制引发神经元细胞损伤（γ-氨基丁酸摄取受损和神经元丢失）。用免疫抑制细胞因子白细胞介素-4（IL-4）对细胞共培养体系进行预处理，以剂量依赖的方式预防了活化小胶质细胞诱导的神经元细胞损伤。发现IL-4发挥其神经保护作用的机制涉及抑制小胶质细胞的γ干扰素预处理，随后减少TNF-α和一氧化氮的产生。
