Poly(I:C) promotes TNFα/TNFR1-dependent oligodendrocyte death in mixed glial cultures.
Poly(I:C) promotes TNFα/TNFR1-dependent oligodendrocyte death in mixed glial cultures.
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DOI：
10.1186/1742-2094-8-89
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发表时间：
2011-08-03
影响因子：
9.3
通讯作者：
Li J
中科院分区：
文献类型：
--
作者：
Steelman AJ;Li J
通过toll样受体（TLRs）和其他细胞内病原体识别受体激活胶质细胞，促进潜在毒性急性期反应物（如TNFα和一氧化氮）释放到细胞外空间。因此，长时间的神经胶质激活，被认为发生在中枢神经系统的持续病毒感染期间，可能有助于神经退行性变和脱髓鞘。然而，病毒诱导的胶质细胞活化对少突胶质细胞的影响尚不完全清楚。为了确定胶质细胞激活对少突胶质细胞活力的影响，我们用RNA病毒模拟聚（I:C）和其他TLR配体处理了从新生大鼠或小鼠分离的初级胶质细胞培养物。western blot检测TLR3的表达。采用RT-PCR、ELISA和细胞内细胞因子染色检测细胞因子水平。用Alamar蓝法和免疫细胞化学法测定少突胶质细胞前体（preOL）活力。用poly（I:C）刺激混合胶质细胞培养可激活小胶质细胞，产生tnf - α和预ol毒性。poly（I:C）的这种毒性作用是间接的，因为尽管preOL表达TLR3，但它在纯培养物中未能影响preOL的活力。在TNFα或TNFR1缺失的混合胶质培养物中，Poly（I:C）诱导的前醇醚醇丢失被消除，这表明TNFα/TNFR1信号是Poly（I:C）毒性所必需的。此外，尽管小胶质细胞和星形胶质细胞都表达功能性TLR3，但在培养中只有小胶质细胞产生TNFα。与这些发现一致，其他TLR激动剂同样在混合胶质培养中引发TNFα产生和前ol毒性。聚（I:C）激活小胶质细胞可促进依赖TNFα/ tnfr1的少突胶质细胞死亡。这些数据表明，在中枢神经系统持续的病毒感染过程中，小胶质细胞TNFα可能对少突胶质细胞有害。
Activation of glial cells via toll-like receptors (TLRs) and other intracellular pathogen recognition receptors promotes the release of potentially toxic acute phase reactants such as TNFα and nitric oxide into the extracellular space. As such, prolonged glial activation, as is thought to occur during a persistent viral infection of the CNS, may contribute to both neurodegeneration and demyelination. However, the effects of virus-induced glial activation on oligodendrocytes are not fully understood. To determine the effects of glial activation on oligodendrocyte viability we treated primary glial cultures isolated from neonatal rats or mice with the RNA viral mimic poly(I:C) and in some cases other TLR ligands. TLR3 expression was determined by western blot. Cytokine levels were measured by RT-PCR, ELISA, and intracellular cytokine staining. Oligodendrocyte precursor (preOL) viability was determined by Alamar blue assays and immunocytochemistry. Stimulation of mixed glial cultures with poly(I:C) resulted in microglia activation, TNFα production and preOL toxicity. This toxic effect of poly(I:C) was indirect as it failed to affect preOL viability in pure cultures despite the fact that preOLs express TLR3. Poly(I:C)-induced loss of preOLs was abolished in TNFα or TNFR1 deficient mixed glial cultures, suggesting that TNFα/TNFR1 signaling is required for poly(I:C) toxicity. Furthermore, although both microglia and astrocytes express functional TLR3, only microglia produced TNFα in culture. Consistent with these findings, other TLR agonists similarly triggered TNFα production and preOL toxicity in mixed glial cultures. Activation of microglia by poly(I:C) promotes TNFα/TNFR1-dependent oligodendroglial cell death. These data indicate that during an ongoing viral infection of the CNS, microglial TNFα may be detrimental to oligodendrocytes.
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影响因子：
6.2
作者：
Carpentier, Pamela A.;Williams, Bryan R.;Miller, Stephen D.
通讯作者：
Miller, Stephen D.
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：
6.2
作者：
Bsibsi, M;Persoon-Deen, C;Van Noort, JM
通讯作者：
Van Noort, JM
影响因子：
6.2
作者：
Carpentier, PA;Begolka, WS;Miller, SD
通讯作者：
Miller, SD
影响因子：
4.8
作者：
Glezer, Isaias;Lapointe, Amelie;Rivest, Serge
通讯作者：
Rivest, Serge