Water-soluble chitosan inhibits the production of pro-inflammatory cytokine in human astrocytoma cells activated by amyloid β peptide and interieukin-1β
Water-soluble chitosan inhibits the production of pro-inflammatory cytokine in human astrocytoma cells activated by amyloid β peptide and interieukin-1β
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DOI：
10.1016/s0304-3940(02)00066-6
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发表时间：
2002-03-15
影响因子：
2.5
通讯作者：
Kim, HM
中科院分区：
文献类型：
--
作者：
Kim, MS;Sung, MJ;Kim, HM
与β-淀粉样蛋白（Abeta）和白细胞介素-1 β（IL-1 β）相关的慢性炎症反应是阿尔茨海默病（AD）的病理学原因。星形胶质细胞是中枢神经系统的主要神经胶质细胞，并且积极参与AD中的马槟榔碱介导的事件。为了研究水溶性壳聚糖（WSC）的生物学效应，我们检测了IL-1 β和Abeta片段25-35（Abeta[25-35]）刺激的人星形细胞瘤细胞系CCF-STTG 1的细胞毒性、促炎细胞因子和诱导型一氧化氮合酶（iNOS）的产生。在3-[4，5-二甲基噻唑-2-基]-2，5-二苯基四氮唑溴化比色法中，WSC本身对人星形细胞瘤细胞的细胞活力没有影响。采用酶联免疫吸附试验和Western blotting检测WSC对肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）的影响。TNF-α和IL-6的产生由IL-1 β和A β诱导[25-35]，并通过IL-1 β和AP的共刺激协同放大[25-35]。在人星形细胞瘤细胞中，WSC预处理显著抑制促炎细胞因子TNF-α和IL-6的分泌和表达。IL-1 β和Abeta可诱导iNOS的表达[25-35]，WSC处理可部分抑制iNOS的表达。我们首次证明了WSC在人星形胶质细胞中的调节作用，并表明WSC的抗炎作用可能减少和延迟AD病理事件。(C)2002爱思唯尔科学爱尔兰有限公司保留所有权利。
A chronic inflammatory response associated with beta-amyloid (Abeta) and interleukin-1beta (IL-1beta) is responsible for the pathology of Alzheimer's disease (AD). Astrocytes are predominant neuroglial cells of the central nervous system and are actively involved in cytokine-mediated events in AD. To investigate the biological effect of water-soluble chitosan (WSC), we examined cytotoxicity, production of pro-inflammatory cytokines and inducible nitric-oxide synthase (iNOS) on human astrocytoma cell line CCF-STTG1 stimulated with IL-1beta and Abeta fragment 25-35 (Abeta[25-35]). In 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazoliumbromide colorimetric assay, WSC by itself had no effect on cell viability on human astrocytoma cells. The effects of WSC on tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) were evaluated with enzyme-linked immunosorbent assay and Western blotting. The production of TNF-alpha and IL-6 was induced by IL-1beta and Abeta[25-35] and synergistically amplified by the co-stimulation of IL-1beta and AP[25-35]. The secretion and expression of pro-inflammatory cytokines, TNF-alpha and IL-6, was significantly inhibited by pretreatment with WSC in human astrocytoma cells. The expression of iNOS was induced by IL-1beta and Abeta[25-35] and was partially inhibited by treatment with WSC. We demonstrate the regulatory effects of WSC in human astrocytes for the first time and suggest the anti-inflammatory effect of WSC may reduce and delay AD pathologic events. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.