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Toll样受体(TLRs)是由进化上相对保守的蛋白家族构成的一组识别受体,是固有免疫系统的第一道防线。受到微生物配体刺激后,TLRs通过激活各种信号通路引发机体一系列防御反应。TLRs还能被内源性危险信号激活,因此推断神经退行性变也可能通过TLRs激活免疫反应。近来研究发现中枢神经系统表达各种类型的TLRs,但周围神经系统中TLRs的表达形式尚无定论。本研究结果显示,施万细胞上表达大量TLRs,主要为TLR3和TLR4。感觉神经元和运动神经元上几乎没有TLRs表达。对NF-κB信号通路的检测显示,施万细胞上所有的TLRs都是有功能的,可被细菌脂蛋白(TLR1/TLR2配体)激活,产生强烈反应。静息状态下,坐骨神经上TLRs的表达形式与施万细胞相似,主要为TLR3、TLR4和TLR7,可能在免疫监督中扮演重要角色。通过显微外科方式对坐骨神经造成急性神经退行性变后,诱导TLR1大量表达,其它TLRs的表达水平无变化。综上所述,本研究结果显示,施万细胞可能在周围神经中扮演类似中枢神经系统小胶质细胞的角色。急性神经退行性变诱导TLR表达变化,说明在分布于周围神经的TLRs在静息状态和激活状态下具有不同功能。
Toll-like receptors (TLRs) are a group of recognition receptors made up of a relatively conserved family of proteins that are the first line of defense of the innate immune system. After being stimulated by microbial ligands, TLRs trigger a series of defense responses by activating various signaling pathways. TLRs can also be activated by endogenous dangerous signals, so it is concluded that neurodegeneration may also activate immune responses via TLRs. Recent studies have found that the central nervous system expresses various types of TLRs, but the expression pattern of TLRs in the peripheral nervous system is inconclusive. The results of this study show that a large number of TLRs are expressed on Schwann cells, mainly TLR3 and TLR4. There is almost no TLRs expression in sensory neurons and motor neurons. Detection of the NF-κB signaling pathway revealed that all TLRs on Schwann cells are functional and can be activated by bacterial lipoproteins (TLR1 / TLR2 ligand) and produce a strong response. Resting state, the expression of TLRs on the sciatic nerve similar to Schwann cells, mainly TLR3, TLR4 and TLR7, may play an important role in immune surveillance. Acute neurodegeneration in the sciatic nerve was induced by microsurgery, which induced a large amount of TLR1 expression. The expression level of other TLRs did not change. In summary, the results of this study show that Schwann cells may play a similar role in central nervous system microglia in peripheral nerves. Acute neurodegeneration induces changes in TLR expression, indicating that TLRs distributed in the peripheral nerves have different functions at rest and in activation.