Department of Oral Anatomy, College of Dentistry, Gangneung-Wonju National University, Gangneung 210-702, South Korea.
Neurochem Res. 2011 Dec;36(12):2417-26. doi: 10.1007/s11064-011-0569-0. Epub 2011 Aug 13.
Innate immune system is very important to modulate the host defense against a large variety of pathogens. Toll-like receptors (TLRs) play a key role in controlling innate immune response. Among TLRs, TLR4 is a specific receptor for lipopolysaccharide and associated with the release of pro-inflammatory cytokines. In the present study, we investigated ischemia-related changes of TLR4 immunoreactivity and its protein level, and nuclear factor κB (NF-κB) p65 immunoreactivity regarding inflammatory responses in the hippocampal CA1 region after 5 min of transient cerebral ischemia to identify the correlation between transient ischemia and inflammation. In the sham-operated group, TLR4 immunoreactivity was easily detected in pyramidal neurons of the hippocampal CA1 region (CA1). TLR4 immunoreactivity in pyramidal neurons was distinctively decreased after ischemia/reperfusion (I/R); instead, based on double immunofluorescence study, TLR4 immunoreactivity was expressed in non-pyramidal neurons and astrocytes from 2 days postischemia. In addition, TLR4 protein level was lowest at 1 day postischemia and highest 4 days after I/R. On the other hand, NF-κB p65 immunoreactivity was not detected in the CA1 of the sham-operated group, and NF-κB p65 immunoreactivity was not observed until 1 day after I/R. However, NF-κB p65 immunoreactivity began to be expressed in astrocytes at 2 days postischemia, and the immunoreactivity was strong 4 days postischemia. Our results indicate that TLR4 and NF-κB p65 immunoreactivity are changed in CA1 pyramidal neurons and newly expressed in astrocytes, not in microglia, in the CA1 region after transient cerebral ischemia.
先天免疫系统对于调节宿主防御各种病原体至关重要。Toll 样受体（TLR）在控制先天免疫反应中发挥关键作用。在 TLR 中，TLR4 是脂多糖的特异性受体，与促炎细胞因子的释放有关。本研究旨在探讨短暂性脑缺血后海马 CA1 区 TLR4 免疫反应及其蛋白水平和核因子 κB（NF-κB）p65 免疫反应的变化与缺血相关炎症反应的关系，以确定短暂性缺血与炎症之间的相关性。在假手术组中，TLR4 免疫反应在海马 CA1 区（CA1）的锥体细胞中很容易检测到。缺血再灌注（I/R）后，TLR4 免疫反应明显降低；相反，基于双重免疫荧光研究，TLR4 免疫反应在缺血后 2 天在非锥体细胞和星形胶质细胞中表达。此外，TLR4 蛋白水平在缺血后 1 天最低，4 天后最高。另一方面，NF-κB p65 免疫反应在假手术组的 CA1 区未检测到，仅在 I/R 后 1 天观察到 NF-κB p65 免疫反应。然而，NF-κB p65 免疫反应在缺血后 2 天开始在星形胶质细胞中表达，4 天后免疫反应强烈。我们的结果表明，在短暂性脑缺血后，TLR4 和 NF-κB p65 免疫反应在 CA1 锥体神经元中发生变化，并在星形胶质细胞中重新表达，而不是在小胶质细胞中表达。
