Early increase in mRNA levels of pro-inflammatory cytokines and their interactions in the mouse hippocampus after transient global ischemia
Early increase in mRNA levels of pro-inflammatory cytokines and their interactions in the mouse hippocampus after transient global ischemia
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DOI：
10.1016/j.neulet.2005.08.072
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发表时间：
2006-01
影响因子：
2.5
通讯作者：
Yuyan Zhu;Kuniaki Saito;Yuki Murakami;M. Asano;Y. Iwakura;M. Seishima
中科院分区：
文献类型：
--
作者：
Yuyan Zhu;Kuniaki Saito;Yuki Murakami;M. Asano;Y. Iwakura;M. Seishima
有令人信服的证据表明，细胞因子参与脑缺血后的炎症反应，但促炎细胞因子肿瘤坏死因子(TNF)-α、白细胞介素(IL)-1β和IL-6在缺血再灌注早期的相互作用尚不完全清楚。在本研究中，我们利用实时聚合酶链反应检测了C57BL/6J野生型（WT）和TNF-α、IL-1α/β或IL-6基因敲除（KO）小鼠双侧颈总动脉闭塞30min后缺血海马中促炎细胞因子的早期mRNA表达。与假手术小鼠相比，缺血WT小鼠的促炎因子TNF-α、IL-6和IL-1β mRNA表达明显增加。缺血后TNF-α、IL-1β和IL-6分别在3 ~ 24小时、12小时和6 ~ 24小时升高。然而，缺血基因KO小鼠的细胞因子mrna的时间表达模式与WT小鼠不同。缺血再灌注后，IL-6 KO小鼠TNF-α mRNA的时间表达模式与WT小鼠相似，且各时间点水平均低于WT小鼠。IL-1β mRNA水平在缺血TNF-α KO小鼠和IL-6 KO小鼠中非常低，尽管在24h均观察到一个小峰值。缺血WT和TNF-α KO小鼠各时间点IL-6 mRNA水平均显著上调；然而，IL-1α/β KO小鼠的峰值延迟了12小时。综上所述，本研究提示小鼠海马短暂性全脑缺血后细胞因子水平的快速升高是相互依赖、相互作用的，可能是相互调节的。
There is convincing evidence that cytokines are involved in the inflammatory response following cerebral ischemia, but the interactions among the pro-inflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-1β and IL-6 in the early stage of ischemic reperfusion are not yet completely understood. In this study, we examined the early mRNA expressions of pro-inflammatory cytokines in the ischemic hippocampus after 30min of bilateral common carotid artery occlusion in C57BL/6J wild-type (WT) and TNF-α, IL-1α/β or IL-6 gene knockout (KO) mice utilizing real-time polymerase chain reaction. The mRNA expressions of the pro-inflammatory cytokines TNF-α, IL-6 and IL-1β were significantly induced in ischemic WT mice compared with in the sham-operated mice. These increases peaked at 3 to 24h for TNF-α, at 12h for IL-1β, and at 6 to 24h for IL-6 after ischemia. The pattern of temporal expression of the cytokine mRNAs in ischemic gene KO mice, however, differed from that in WT mice. The TNF-α mRNA expression showed a similar temporal expression pattern in IL-6 KO mice compared to in WT mice following ischemic reperfusion, and the levels at all time points were lower than in WT mice. The IL-1β mRNA level was very low in ischemic TNF-α KO mice and IL-6 KO mice in spite of a small peak observed in both at 24h. The IL-6 mRNA level was significantly upregulated at all time points in both ischemic WT and TNF-α KO mice; however, the peak was delayed by 12-h in IL-1α/β KO mice. In conclusion, the present study indicates that the rapid increases in cytokine levels are interdependent, interactive, and possibly modulate each other in the mouse hippocampus after transient global ischemia.