Oncostatin M and the interleukin-6 and soluble interleukin-6 receptor complex regulate α1-antichymotrypsin expression in human cortical astrocytes
Oncostatin M and the interleukin-6 and soluble interleukin-6 receptor complex regulate α1-antichymotrypsin expression in human cortical astrocytes
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DOI：
10.1074/jbc.273.7.4112
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发表时间：
1998-02-13
影响因子：
4.8
通讯作者：
Travis, J
中科院分区：
文献类型：
--
作者：
Kordula, T;Rydel, RE;Travis, J
α（1）-抗胰凝乳蛋白酶（ACT）是一种在大脑中表达的急性期蛋白，在阿尔茨海默病期间特异性与β淀粉样蛋白共定位。我们分析了培养的人皮质星形胶质细胞对各种细胞因子和生长因子的反应中ACT的合成。制瘤素M（OSM）和白细胞介素（IL）-1 β是ACT mRNA表达的有效刺激物，而肿瘤坏死因子-α具有中等活性，IL-6和白血病抑制因子（LIF）无效。OSM而不是LIF或IL-6刺激ACT表达的发现表明，人星形胶质细胞表达“特异性”OSM受体，而不是IL-6或LIF受体。然而，用可溶性IL-6受体（sIL-6 R）、IL-6复合物共同处理人星形胶质细胞确实导致ACT表达的强刺激。当ACT基因被克隆后，我们发现OSM或IL-6.sIL-6 R复合物可与STAT 1和STAT 3（信号转导子和转录激活子）结合。这些结果表明，OSM或IL-6.sIL-6复合物可调节ACT在人星形胶质细胞中的表达，从而直接或间接地参与阿尔茨海默病的发病。
alpha(1)-Antichymotrypsin (ACT) is an acute phase protein expressed in the brain which specifically colocalizes with amyloid-beta during Alzheimer's disease, We analyzed ACT synthesis in cultured human cortical astrocytes in response to various cytokines and growth factors. Oncostatin M (OSM) and interleukin (IL)-1 beta were potent stimulators of ACT mRNA expression, whereas tumor necrosis factor-alpha had modest activity, and IL-6 and leukemia inhibitory factor (LIF) were ineffective. The finding that OSM, but not LIF or IL-6, stimulated ACT expression suggests that human astrocytes express a "specific" OSM receptor, but not IL-6 or LIF receptors, However, cotreatment of human, astrocytes with soluble IL-6 receptor (sIL-6R).IL-6 complex did result In potent stimulation of ACT expression. When the human ACT gene was cloned, two elements binding STAT1 and STAT3 (signal transducer and activator of transcription) in response to OSM or IL-6.sIL-6R complexes could be identified and characterized, Taken together, these findings indicate that OSM or IL-6.sIL-6 complexes may regulate ACT expression in human astrocytes and thus directly or indirectly contribute to title pathogenesis of Alzheimer's disease.