The antimicrobial protein, CAP37, is upregulated in pyramidal neurons during Alzheimer's disease.
The antimicrobial protein, CAP37, is upregulated in pyramidal neurons during Alzheimer's disease.
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DOI：
10.1007/s00418-015-1347-x
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发表时间：
2015-10
影响因子：
2.3
通讯作者：
Anne Pereira H
中科院分区：
文献类型：
--
作者：
Brock AJ;Kasus-Jacobi A;Lerner M;Logan S;Adesina AM;Anne Pereira H
炎症是阿尔茨海默病(AD)的一个明确定义的因素。迫切需要确定导致神经炎症的分子，以便设计出预防免疫介导的神经毒性的治疗方法。37 kDa的阳离子抗菌蛋白(CAP37)是中性粒细胞(PMN)结构性表达的炎症介质。除了抗生素活性，CAP37对小胶质细胞也有免疫调节作用。我们假设CAP37介导了与AD相关的神经炎症。然而，中性粒细胞通常与AD的病理无关。因此，本研究旨在确定AD患者脑内CAP37的非中性粒细胞来源(S)。用免疫组织化学方法(IHC)分析患者和年龄匹配的对照组脑组织中CAP37的表达。用肿瘤坏死因子-α(TNF-α)或淀粉样蛋白-1受体40(A-β1−40，A-β)处理原代培养的人神经元，并进行免疫组化分析，以确定诱发AD的因素。用Western blotting和定量逆转录聚合酶链式反应(qRT-PCR)检测CAP37在神经元和脑组织中的表达。免疫组织化学染色显示AD患者颞叶和顶叶皮质神经元以及CA3和CA4神经元均有CAP37表达。与年龄匹配的对照组相比，AD组神经元中CAP37的表达增多。QRT-PCR和Western blotting显示，CAP37在AD颞叶的转录和蛋白表达增加，这是一个在AD中受到高度影响的大脑区域。定量逆转录聚合酶链式反应证实CAP37在神经元中表达。肿瘤坏死因子-α和A-β增加CAP37神经元的表达。这些发现支持我们的假设，即神经元CAP37可能调节AD的神经炎性反应。
Inflammation is a well-defined factor in Alzheimer’s disease (AD). There is a strong need to identify the molecules contributing to neuroinflammation so that therapies can be designed to prevent immune-mediated neurotoxicity. The cationic antimicrobial protein of 37 kDa (CAP37) is an inflammatory mediator constitutively expressed in neutrophils (PMNs). In addition to antibiotic activity, CAP37 exerts immunomodulatory effects on microglia. We hypothesize that CAP37 mediates the neuroinflammation associated with AD. However, PMNs are not customarily associated with the pathology of AD. This study was therefore designed to identify non-neutrophilic source(s) of CAP37 in brains of AD patients. Brain tissues from patients and age-matched controls were analyzed for CAP37 expression using immunohistochemistry (IHC). To determine factors that induce CAP37 in AD, HCN-1A primary human neurons were treated with tumor necrosis factor-alpha (TNF-α) or amyloid β1−40 (Aβ) and analyzed by IHC. Western blotting and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were used to confirm CAP37 expression in neurons and brain tissues. IHC revealed CAP37 in cortical neurons in temporal and parietal lobes as well as CA3 and CA4 hippocampal neurons in patients with AD. CAP37 was found in more neurons in AD patients compared with age-matched controls. qRT-PCR and Western blotting showed an increase in CAP37 transcript and protein in the AD temporal lobe, a brain region that is highly impacted in AD. qRT-PCR observations confirmed CAP37 expression in neurons. TNF-α and Aβ increased neuronal expression of CAP37. These findings support our hypothesis that neuronal CAP37 may modulate the neuroinflammatory response in AD.