School of Basic Medicine, Peking Union Medical College & Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing 100005, China.
Curr Alzheimer Res. 2012 Oct;9(8):953-61. doi: 10.2174/156720512803251093.
A chronic inflammatory response possibly mediated by Amyloid β (Aβ) is believed to be a major factor in the pathology of Alzheimer's disease (AD). Studies suggest that the mediators of the inflammatory response, which might contribute to brain damage, involve cytokines, such as IL-1β. IL-1β could play an important part in the development of pathologic conditions. There is also an endogenous interleukin-1 receptor antagonist (IL-1RA) in IL-1 family, which could prevent the actions of IL-1β by competing for receptor binding without inducing any signal transduction. Therefore, the balance of IL-1β vs IL-1RA is a critical parameter in determining not only whether excessive host inflammation will occur, but also the degree of subsequent host cell damage and associated toxicity. In our previous study, it has been determined that the anti-inflammatory action of Gossypium herbaceam L. extracts (GHE) was involved in its neuroprotection. However, the effects of GHE on IL-1β and IL-1RA have not been clearly defined in the experimental rat model of AD induced by Aβ. Therefore, the current study is performed to evaluate whether GHE could affect the disequilibrium of IL-1RA/IL-1β ratio in the hippocampus of rats after Aβ treatment. Subsequently, we further identify that GHE could efficaciously promote Akt and GSK3β phosphorylation, and thereby contribute to IL-1β release decrease as well as a concurrent increase in the level of IL-1RA through NF-κB and MAPK pathways. As a consequence, GHE is potentially beneficial to maintain the endogenous IL-1RA/ IL-1β balance in the hippocampus of rats and it might be a potential agent to ameliorate inflammatory process in AD.
一种由淀粉样蛋白β(Aβ)介导的慢性炎症反应被认为是阿尔茨海默病(AD)病理的主要因素。研究表明,炎症反应的介质,可能导致大脑损伤,涉及细胞因子,如白细胞介素 1β。白细胞介素 1β 在病理性疾病的发展中可能起着重要作用。白细胞介素 1 家族中也存在内源性白细胞介素 1 受体拮抗剂(IL-1RA),它可以通过竞争受体结合而不诱导任何信号转导来阻止 IL-1β 的作用。因此,IL-1β 与 IL-1RA 的平衡是决定是否会发生过度的宿主炎症以及随后宿主细胞损伤和相关毒性程度的关键参数。在我们之前的研究中,已经确定棉花草提取物(GHE)的抗炎作用与其神经保护作用有关。然而,在 Aβ 诱导的 AD 实验大鼠模型中,GHE 对 IL-1β 和 IL-1RA 的影响尚未明确界定。因此,目前的研究旨在评估 GHE 是否可以影响 Aβ 处理后大鼠海马中 IL-1RA/IL-1β 比值的失衡。随后,我们进一步发现 GHE 可以通过 NF-κB 和 MAPK 通路有效促进 Akt 和 GSK3β 的磷酸化,从而有助于降低 IL-1β 的释放,并同时增加 IL-1RA 的水平。因此,GHE 有可能有利于维持大鼠海马中内源性 IL-1RA/IL-1β 的平衡,并且可能是改善 AD 中炎症过程的潜在药物。