Corticosteroids reverse cytokine-induced block of survival and differentiation of oligodendrocyte progenitor cells from rats.
Corticosteroids reverse cytokine-induced block of survival and differentiation of oligodendrocyte progenitor cells from rats.
复制标题
皮质类固醇反向细胞因子诱导的生存和分化的少突胶质细胞祖细胞与大鼠的分化。
DOI：
10.1186/1742-2094-5-39
复制
发表时间：
2008-09-22
影响因子：
9.3
通讯作者：
Berger, Richard
中科院分区：
文献类型：
--
作者：
Mann, Stefan A.;Versmold, Beatrix;Marx, Romy;Stahlhofen, Sabine;Dietzel, Irmgard D.;Heumann, Rolf;Berger, Richard
脑室周围白质软化症（PVL）是早产的常见并发症。由感染或缺血激活的星形胶质细胞和小胶质细胞释放的促炎细胞因子，如干扰素-γ（IFN-γ）和肿瘤坏死因子α（TNF-α），先前已显示会损害少突胶质细胞祖细胞的存活和成熟，因此可被认为是导致这种疾病产生的潜在因素。本研究的第一个目标是调查是否暴露的少突胶质细胞前体细胞因子逮捕的成熟的离子电流平行髓鞘蛋白和形态成熟的影响。其次，在寻找代理人，可以保护分化少突胶质细胞前体细胞从尼古丁诱导的损伤，我们研究了皮质类固醇与促炎细胞因子的共同应用对随后的生存和分化的少突胶质细胞祖细胞的影响。为了排除从其他细胞类型释放的因子的影响，将少突胶质细胞前体的纯化培养物暴露于细胞因子和/或类固醇，并允许在培养物中再分化6天。用电容记录和扫描离子电导显微镜研究了膜表面的变化。采用全细胞膜片钳记录研究Na+和K+电流。髓鞘特异性蛋白质的表达进行了研究，使用蛋白质印迹和前体细胞进行了鉴定，使用免疫染色与A2 B5抗体。存活的IFN-γ和TNF-α处理的细胞在分化培养基中6天后继续维持未成熟细胞特有的电压激活的Na+和K+电流。皮质酮、二氢皮质酮和最显著的地塞米松抵消了IFN-γ和TNF-α对细胞存活、A2 B5免疫染色和髓鞘碱性蛋白表达的有害作用。最有效的皮质类固醇测试，地塞米松，被证明可以抵消细胞因子对膜表面延伸和电容的影响。此外，地塞米松的共同应用阻断了80%的前体细胞中烟碱诱导的内向整流钾电流的下调，并恢复了烟碱阻断的电压激活的Na+和K+电流的下调，在随后的分化。我们的研究结果表明，用炎性细胞因子TNF-α和IFN-γ处理少突胶质细胞前体在电压门控离子电流的分化水平上阻断了少突胶质细胞前体的分化。在细胞因子应用时与皮质类固醇的共治疗在相当程度上恢复了少突胶质细胞在形态学、髓鞘蛋白以及离子电流成熟水平上的存活和分化，这表明了对精氨酸损伤的未成熟少突胶质细胞的功能恢复的选择。
Periventricular leukomalacia (PVL) is a frequent complication of preterm delivery. Proinflammatory cytokines, such as interferon-γ (IFN-γ) and tumor necrosis factor α (TNF-α) released from astrocytes and microglia activated by infection or ischemia have previously been shown to impair survival and maturation of oligodendrocyte progenitors and could thus be considered as potential factors contributing to the generation of this disease. The first goal of the present study was to investigate whether exposure of oligodendrocyte precursors to these cytokines arrests the maturation of ion currents in parallel to its effects on myelin proteins and morphological maturation. Secondly, in the search for agents, that can protect differentiating oligodendrocyte precursor cells from cytokine-induced damage we investigated effects of coapplications of corticosteroids with proinflammatory cytokines on the subsequent survival and differentiation of oligodendrocyte progenitor cells. To exclude influences from factors released from other cell types purified cultures of oligodendrocyte precursors were exposed to cytokines and/or steroids and allowed to differentiate for further 6 days in culture. Changes in membrane surface were investigated with capacitance recordings and Scanning Ion Conductance Microscopy. Na+- and K+- currents were investigated using whole cell patch clamp recordings. The expression of myelin specific proteins was investigated using western blots and the precursor cells were identified using immunostaining with A2B5 antibodies. Surviving IFN-γ and TNF-α treated cells continued to maintain voltage-activated Na+- and K+ currents characteristic for the immature cells after 6 days in differentiation medium. Corticosterone, dihydrocorticosterone and, most prominently dexamethasone, counteracted the deleterious effects of IFN-γ and TNF-α on cell survival, A2B5-immunostaining and expression of myelin basic protein. The most potent corticosteroid tested, dexamethasone, was shown to counteract cytokine effects on membrane surface extension and capacitance. Furthermore, coapplication of dexamethasone blocked the cytokine-induced downregulation of the inwardly rectifying potassium current in 80% of the precursor cells and restored the cytokine-blocked down-regulation of the voltage activated Na+- and K+ currents during subsequent differentiation. Our results show that treatment of oligodendrocyte precursors with the inflammatory cytokines TNF-α and IFN-γ block the differentiation of oligodendrocyte precursors at the level of the differentiation of the voltage-gated ion currents. Co-treatment with corticosteroids at the time of cytokine application restores to a considerable extent survival and differentiation of oligodendrocytes at the level of morphological, myelin protein as well as ion current maturation suggesting the option for a functional restoration of cytokine-damaged immature oligodendrocytes.
登录
查看更多内容
影响因子：
3.4
作者：
Agresti, C;DUrso, D;Levi, G
通讯作者：
Levi, G
影响因子：
4.8
作者：
du Plessis, AJ;Volpe, JJ
通讯作者：
Volpe, JJ
影响因子：
3.3
作者：
Cammer, W;Zhang, H
通讯作者：
Zhang, H
影响因子：
5.5
作者：
CHIU, SY;WILSON, GF
通讯作者：
WILSON, GF
影响因子：
4.8
作者：
Evans-Storms, RB;Cidlowski, JA
通讯作者：
Cidlowski, JA