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首页> 外文期刊>The Journal of Neuroscience: The Official Journal of the Society for Neuroscience >Microglial phagocytosis induced by fibrillar beta-amyloid and IgGs are differentially regulated by proinflammatory cytokines.
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Microglial phagocytosis induced by fibrillar beta-amyloid and IgGs are differentially regulated by proinflammatory cytokines.

机译：原纤维β淀粉样蛋白和IgG诱导的小胶质细胞吞噬由促炎细胞因子差异调节。

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摘要

Microglia undergo a phenotypic activation in response to fibrillar beta-amyloid (fAbeta) deposition in the brains of Alzheimer's disease (AD) patients, resulting in their elaboration of inflammatory molecules. Despite the presence of abundant plaque-associated microglia in the brains of AD patients and in animal models of the disease, microglia fail to efficiently clear fAbeta deposits. However, they can be induced to do so during Abeta vaccination therapy attributable to anti-Abeta antibody stimulation of IgG receptor (FcR)-mediated phagocytic clearance of Abeta plaques. We report that proinflammatory cytokines attenuate microglial phagocytosis stimulated by fAbeta or complement receptor 3 and argue that this may, in part, underlie the accumulation of fAbeta-containing plaques within the AD brain. The proinflammatory suppression of fAbeta-elicited phagocytosis is dependent on nuclear factor kappaB activation. Significantly, the proinflammatory cytokines do not inhibit phagocytosis elicited by antibody-mediated activation of FcR, which may contribute to the efficiency of Abeta vaccination-based therapy. Importantly, the proinflammatory suppression of fAbeta phagocytosis can be relieved by the coincubation with anti-inflammatory cytokines, cyclooxygenase inhibitors, ibuprofen, or an E prostanoid receptor antagonist, suggesting that proinflammatory cytokines induce the production of prostaglandins, leading to an E prostanoid receptor-dependent inhibition of phagocytosis. These findings support anti-inflammatory therapies for the treatment of AD.
机译：小胶质细胞响应于阿尔茨海默氏病（AD）患者大脑中的原纤维β-淀粉样蛋白（fAbeta）沉积而发生表型激活，从而导致炎症分子的产生。尽管在AD患者的大脑和该疾病的动物模型中存在大量的斑块相关小胶质细胞，但小胶质细胞无法有效清除fAbeta沉积物。但是，在Abeta疫苗治疗期间，可以诱导它们这样做，这归因于抗Abeta抗体对IgG受体（FcR）介导的Abeta斑块吞噬清除的刺激。我们报告说，促炎细胞因子减弱了由fAbeta或补体受体3刺激的小胶质细胞吞噬作用，并认为这可能部分是AD脑内含fAbeta的斑块积累的基础。 fAbeta引起的吞噬作用的促炎性抑制取决于核因子kappaB的激活。重要的是，促炎细胞因子不抑制由抗体介导的FcR激活引起的吞噬作用，这可能有助于提高基于Abeta疫苗的治疗的效率。重要的是，可通过与抗炎细胞因子，环氧合酶抑制剂，布洛芬或E类前列腺素受体拮抗剂共同孵育来缓解fAbeta吞噬作用的促炎抑制作用，这表明促炎细胞因子可诱导前列腺素的产生，从而导致E类前列腺素受体依赖性抑制吞噬作用。这些发现支持用于AD治疗的抗炎疗法。

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