Cultures of astrocytes and microglia express interleukin 18
Cultures of astrocytes and microglia express interleukin 18
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DOI：
10.1016/s0169-328x(99)00034-0
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发表时间：
1999-04-06
期刊：
影响因子：
--
通讯作者：
Joh, TH
中科院分区：
文献类型：
--
作者：
Conti, B;Park, LCH;Joh, TH
白细胞介素18（IL-18或干扰素-γ诱导因子）是最近发现的促炎细胞因子和细胞介导的免疫应答的强刺激剂。IL-18由几种来源产生，包括单核细胞/巨噬细胞、角质形成细胞和肾上腺皮质的网状内皮细胞和束状内皮细胞。IL-18存在于脑中，但其在CNS中的细胞来源从未被研究过。用小胶质细胞、星形胶质细胞和海马神经元的原代培养物测试脑中IL-18的存在及其对刺激的响应。IL-18 mRNA在星形胶质细胞和小胶质细胞中表达，而在神经元中不表达。内毒素脂多糖（LPS）对星形胶质细胞IL-18无影响，但可显著增加小胶质细胞IL-18 mRNA的表达。IL-18蛋白在星形胶质细胞中组成型表达，在小胶质细胞中被LPS诱导表达。评估白细胞介素-1 β转化酶（ICE）（一种活化酶）和半胱天冬酶3（CPP 32）（一种失活酶）的水平，以研究培养细胞中是否存在适当的加工酶。ICE在小胶质细胞和星形胶质细胞中以组成性水平存在，表明这些细胞类型可以产生和分泌成熟的IL-18。在两种细胞类型中均检测不到CPP 32的活性形式，表明不存在IL-1 s的降解途径。本研究结果表明，小胶质细胞和星形胶质细胞是脑IL-1的来源，并为脑中产生的细胞因子家族增加了新成员。(C)1999 Elsevier Science B. V.保留所有权利。
Interleukin 18 (IL-18 or interferon-gamma inducing factor) is a recently discovered pro-inflammatory cytokine and powerful stimulator of the cell-mediated immune response. IL-18 is produced by several sources including monocytes/macrophages, keratinocytes and the zona reticularis and zona fasciculata of the adrenal cortex. IL-18 occurs in brain but its cellular source in the CNS has never been investigated. The presence of IL-18 and its response to stimulation in the brain was tested with primary cultures of microglia, astrocytes and hippocampal neurons. IL-18 mRNA was present in astrocytes and microglia, but not in neurons. The endotoxin lipopolysaccharide (LPS) did not affect IL-18 in astrocytes, but LPS robustly increased IL-18 mRNA in microglia. IL-18 protein was constitutively expressed in astrocytes and induced in microglia by LPS. The levels of interleukin-1 beta converting enzyme (ICE), an activating enzyme, and caspase 3 (CPP32), an inactivating enzyme, were assessed to investigate the presence of the appropriate processing enzymes in the cultured cells. ICE was present at constitutive levels in microglia and astrocytes suggesting that these cell types may produce and secrete matured IL-18. Active forms of CPP32 were not detectable in either cell type indicating the absence of a degradative pathway of IL-ls. The present results demonstrate that microglia and astrocytes are sources of brain IL-ls and add a new member to the family of cytokines produced in the brain. (C) 1999 Elsevier Science B.V. All rights reserved.