IL-10 production is reduced by hypothermia but augmented by hyperthermia in rat microglia
IL-10 production is reduced by hypothermia but augmented by hyperthermia in rat microglia
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DOI：
10.1089/neu.2007.0482
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发表时间：
2008-06-01
影响因子：
4.2
通讯作者：
Kakeda, Takahiro
中科院分区：
文献类型：
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作者：
Matsui, Tomohiro;Kakeda, Takahiro
促炎细胞因子和一氧化氮(NO)被认为是加重脑损伤的原因。激活的小胶质细胞在神经元破坏过程中产生这些潜在的细胞毒性因子。低温对神经保护的有益作用被认为部分是由于小胶质细胞抑制了损伤后的炎症因子。然而，潜在的机制仍不清楚。特别是，低温在调节抗炎细胞因子方面的作用尚不清楚。我们检测了改变培养温度是否改变了小胶质细胞产生的细胞因子和NO。将分离的新生大鼠小胶质细胞与1mU g/mL脂多糖(LPS)在低温、常温和高温条件下培养72h，用酶联免疫吸附试验(ELISA)检测培养上清液中IL-6和IL-10的水平。通过比色法测定培养基中积累的亚硝酸根含量来分析NO的产生。与常温相比，低温可减少培养6h内毒素诱导的IL-6的产生。相比之下，高温减少了整个培养过程中IL-6的产生。IL-10的产生在24~72 h被低温抑制，而被高温处理的IL-10的产生在24-72 h时增加，而在整个培养过程中，低温使NO的产生减少，而常温和高温下的NO产生无明显差异。在本研究中，低温可减少脂多糖激活的小胶质细胞产生IL-6、IL-10和NO，提示低温的神经保护作用可能不仅与抑制炎症因子有关，还可能与抗炎因子有关(S)。高温特别增加了这些细胞中IL-10的产生。IL-10产生的这些温度依赖性变化可能暗示了这种细胞因子在低温相关神经元保护和高温相关神经元损伤中的重要临床标志物。
Pro-inflammatory cytokines and nitric oxide (NO) are considered responsible for exacerbating brain injury. Activated microglia produce these potentially cytotoxic factors during neuron destruction. The beneficial effects of hypothermia on neuroprotection are considered to be due, in part, to suppression of post-injury inflammatory factors by microglia. However, the underlying mechanisms remain unclear. In particular, the hypothermia's role in modulating anti-inflammatory cytokines is unknown. We examined whether altering culture temperature modifies microglial production of cytokines and NO. Microglia isolated from neonatal rats were cultured with 1 mu g/mL lipopolysaccharide (LPS) under hypothermic, normothermic, and hyperthermic conditions for 72 h. Interleukin (IL)-6 and IL-10 levels in supernatants were measured by enzyme-linked immunosorbent assay (ELISA). NO production was analyzed by colorimetric assay of nitrite accumulated in the medium. Compared to normothermia, hypothermia decreased LPS-induced IL-6 production at 6 h of culture. In contrast, hyperthermia reduced IL-6 production throughout culture. IL-10 production was reduced by hypothermia but augmented by hyperthermia at 24-72 h. NO production was reduced by hypothermia throughout culture, while no significant differences in NO production were observed between normothermia and hyperthermia. In this study, hypothermia reduced production of IL-6, IL-10, and NO by LPS-activated microglia, suggesting that the neuroprotective effects of hypothermia might involve not only the inhibition of inflammatory factors, but also anti-inflammatory factor(s). Hyperthermia specifically increased IL-10 production in these cells. These temperature-dependent changes in IL-10 production may imply an important clinical marker for this cytokine in hypothermia-related neuronal protection and in hyperthermia-related neuronal injury.