Interleukin 4 induces the apoptosis of mouse microglial cells by a caspase-dependent mechanism.
Interleukin 4 induces the apoptosis of mouse microglial cells by a caspase-dependent mechanism.
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DOI：
10.1016/j.nbd.2011.05.010
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发表时间：
2011-09
影响因子：
6.1
通讯作者：
Iribarren, Pablo
中科院分区：
文献类型：
--
作者：
Soria, Javier A.;Arroyo, Daniela S.;Gaviglio, Emilia A.;Rodriguez-Galan, Maria C.;Wang, Ji Ming;Iribarren, Pablo
小胶质细胞是中枢神经系统（CNS）中的常驻巨噬细胞，并在许多病理条件下被激活。小胶质细胞的活化导致反应性小胶质细胞增生，表现为受影响CNS区域中细胞数量的增加。控制小胶质细胞增生对于防止脑的病理损伤可能是重要的。据报道，2型细胞因子IL-4在脑炎症中具有保护作用。然而，它对小胶质细胞存活的影响还没有很好的了解。在这项研究中，我们报告了IL-4对小鼠小胶质细胞存活的双重作用。在6 h的短期培养中，IL-4可减少星形孢菌素诱导的小胶质细胞死亡。相反，在长期治疗（超过48小时），IL-4增加了原代小鼠小胶质细胞和小胶质细胞系N9的凋亡死亡。机制研究表明，在小胶质细胞中，IL-4增加了裂解的半胱天冬酶3和PARP的水平，PARP是活化的半胱天冬酶3的下游。此外，IL-4下调小胶质细胞的自噬和抗凋亡蛋白Bcl-xL。另一方面，用IL-4预孵育小胶质细胞24 h，减弱了神经毒性肽淀粉样蛋白β 1-42（Aβ42）诱导的细胞死亡。我们的观察表明，IL-4在调节小胶质细胞的存活中具有新的功能，这可能对减少CNS中不期望的炎症反应具有重要意义。
Microglial cells are resident macrophages in the central nervous system (CNS) and become activated in many pathological conditions. Activation of microglial cells results in reactive microgliosis, manifested by an increase in cell number in the affected CNS regions. The control of microgliosis may be important to prevent pathological damage to the brain. The type 2 cytokine IL-4 has been reported to be protective in brain inflammation. However, its effect on microglial cell survival was not well understood. In this study, we report a dual effect of IL-4 on the survival of mouse microglial cells. In a 6 h short term culture, IL-4 reduced the death of microglial cells induced by staurosporine. In contrast, in long term treatment (more than 48 h), IL-4 increased the apoptotic death of both primary mouse microglial cells and a microglial cell line N9. Mechanistic studies revealed that, in microglial cells, IL-4 increased the levels of cleaved caspase 3 and PARP, which is downstream of activated caspase 3. In addition, IL-4 down regulated the autophagy and the antiapoptotic protein Bcl-xL in microglial cells. On the other hand, the pre-incubation of microglial cells with IL-4 for 24 h, attenuated the cell death induced by the neurotoxic peptide amyloid beta 1-42 (Aβ42). Our observations demonstrate a novel function of IL-4 in regulating the survival of microglial cells, which may have important significance in reduction of undesired inflammatory responses in the CNS.
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影响因子：
4.4
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通讯作者：
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