Microglia are the major source of TNF-α and TGF-β1 in postnatal glial cultures; regulation by cytokines, lipopolysaccharide, and vitronectin.
Microglia are the major source of TNF-α and TGF-β1 in postnatal glial cultures; regulation by cytokines, lipopolysaccharide, and vitronectin.
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DOI：
10.1016/j.neuint.2013.04.007
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发表时间：
2013-07
影响因子：
4.2
通讯作者：
Milner R
中科院分区：
文献类型：
--
作者：
Welser-Alves JV;Milner R
中枢神经系统 (CNS) 损伤会导致 TNF-α 和 TGF-β1 的产生增加，这两种细胞因子分别具有促炎或抗炎作用。为了确定星形胶质细胞或小胶质细胞是否表达这些细胞因子，先前的研究使用混合胶质细胞培养物 (MGC) 来代表星形胶质细胞，但认为这些结果不可避免地会因 MGC 内污染小胶质细胞的存在而变得复杂。为了澄清这些细胞因子的细胞来源，我们采用了最近描述的制备无小胶质细胞星形胶质细胞培养物的方法，其中神经干细胞（NSC）分化为星形胶质细胞。使用 ELISA 定量三种类型的胶质细胞培养物（MGC、纯小胶质细胞或纯星形胶质细胞）中细胞因子的产生，结果表明，小胶质细胞而不是星形胶质细胞产生 TNF-α，并且 LPS、IFN-γ 会增加这种表达，玻连蛋白会增加这种表达，但 TGF-β1 会减少这种表达。相比之下，TGF-β1 由小胶质细胞和星形胶质细胞产生，但小胶质细胞的水平高出 10 倍。玻连蛋白可增加小胶质细胞中的 TGF-β1 表达，而 TNF-α 和 LPS 则可在较小程度上增加，但星形胶质细胞 TGF-β1 的表达不受任何测试因素的调节。总之，我们的数据表明，小胶质细胞而不是星形胶质细胞是出生后胶质细胞培养物中 TNF-α 和 TGF-β1 的主要来源，并且小胶质细胞这些拮抗细胞因子的产生受到细胞因子、LPS 和玻连蛋白的严格调节。
Damage to the central nervous system (CNS) leads to increased production of TNF-α and TGF-β1, cytokines that have pro- or anti-inflammatory actions, respectively. To define whether astrocytes or microglia express these cytokines, prior studies have used mixed glial cultures (MGC) to represent astrocytes, thought these results are inevitably complicated by the presence of contaminating microglia within MGC. To clarify the cellular source of these cytokines, here we employed a recently described method of preparing microglia-free astrocyte cultures, in which neural stem cells (NSC) are differentiated into astrocytes. Using ELISA to quantify cytokine production in three types of glial culture: MGC, pure microglia or pure astrocytes, this showed that microglia but not astrocytes, produce TNF-α, and that this expression is increased by LPS, IFN-γ, and to a lesser extent by vitronectin, but decreased by TGF-β1. In contrast, TGF-β1 was produced by microglia and astrocytes, though at 10-fold higher levels by microglia. TGF-β1 expression in microglia was increased by vitronectin and to a lesser extent by TNF-α and LPS, but astrocyte TGF-β1 expression was not regulated by any factor tested. In summary, our data reveal that microglia, not astrocytes are the major source of TNF-α and TGF-β1 in postnatal glial cultures, and that microglial production of these antagonistic cytokines is tightly regulated by cytokines, LPS, and vitronectin.
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影响因子：
15.9
作者：
Kreutzberg, GW
通讯作者：
Kreutzberg, GW
影响因子：
8.3
作者：
Krupinski, J;Kumar, P;Kaluza, J
通讯作者：
Kaluza, J
影响因子：
6.2
作者：
Crocker, Stephen J.;Frausto, Ricardo F.;Whitton, J. Lindsay;Milner, Richard
通讯作者：
Milner, Richard
DOI：
10.1084/jem.170.2.607
发表时间：
1989-08-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Hofman FM;Hinton DR;Johnson K;Merrill JE
通讯作者：
Merrill JE
影响因子：
9.3
作者：
Clausen, Bettina H.;Lambertsen, Kate L.;Finsen, Bente
通讯作者：
Finsen, Bente