TGF-β1 reduces the heterogeneity of astrocytic cyclooxygenase-2 and nitric oxide synthase-2 gene expression in a stimulus-independent manner
TGF-β1 reduces the heterogeneity of astrocytic cyclooxygenase-2 and nitric oxide synthase-2 gene expression in a stimulus-independent manner
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DOI：
10.1016/j.prostaglandins.2007.11.004
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发表时间：
2008-03-01
影响因子：
2.9
通讯作者：
Hewett, Sandra J.
中科院分区：
文献类型：
--
作者：
Hamby, Mary E.;Hewett, James A.;Hewett, Sandra J.
转化生长因子-β 1（TGF-β 1）在几种神经系统疾病/病症中被炎性介质上调，其中其参与病理学或提供保护。通常，TGF-β 1的生物学结果取决于基因表达的变化。最近，我们证明了TGF-β 1通过增加表达NOS-2的群体中星形胶质细胞的数量来增强脂多糖（LPS）加干扰素-γ（IFN-γ）诱导的星形胶质细胞一氧化氮的产生。本研究的目的有两个：（1）通过评估TGF-β 1对另一种促炎基因环氧合酶-2（考克斯-2）的作用，确定这种作用是否更普遍地发生;（2）评估刺激特异性。我们发现TGF-β 1增强了LPS加IFN γ诱导的考克斯-2 mRNA和蛋白表达，使表达考克斯-2的星形胶质细胞数量增加了近两倍。这种效应不是刺激特异性的，因为当IL-1 β或TNF α代替LPS时，TGF-β 1增加了表达考克斯-2和NOS-2蛋白的星形胶质细胞的数量。总的来说，这些结果表明，TGF-β 1通过降低细胞群体中噪声的大小，以混杂的方式增加星形胶质细胞中选择的促炎基因的总体蛋白表达水平。(C)2007爱思唯尔公司All rights reserved.
Transforming growth factor-beta 1 (TGF-beta 1) is upregulated by inflammatory mediators in several neurological diseases/disorders where it either participates in the pathology or provides protection. Often, the biological outcome of TGF-beta 1 is dependent upon changes in gene expression. Recently, we demonstrated that TGF-beta 1 enhances astrocytic nitric oxide production induced by lipopolysaccharide (LPS) plus interferon-gamma (IFN gamma) by increasing the number of astrocytes in a population that express NOS-2. The purpose of this study was twofold: (1) to determine whether this effect occurs more generally by assessing the effect of TGF-beta 1 on another pro-inflammatory gene, cyclooxygenase-2 (COX-2); and (2) to assess stimulus specificity. We found that TGF-beta 1 augmented LPS plus IFN gamma-induced COX-2 mRNA and protein expression, by nearly tripling the number of astrocytes that express COX-2. The effect was not stimulus-specific as TGF-beta 1 enhanced the number of astrocytes that expressed both COX-2 and NOS-2 protein when either IL-1 beta or TNF alpha was used in lieu of LPS. Collectively, these results suggest that TGF-beta 1 augments overall protein expression levels of select pro-inflammatory genes in astrocytes in a promiscuous manner by reducing the magnitude of noise in the cellular population. (C) 2007 Elsevier Inc. All rights reserved.