摘要
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 comprise a family of evolutionary conserved pattern recognition receptors that act as a first defense line in the innate immune system. Upon stimulation with microbial ligands, they orchestrate the induction of a host defense response by activating different signaling cascades. Interestingly, they appear to detect the presence of endogenous signals of danger as well and as such, neurode-generation is thought to trigger an immune response through ligation of TLRs. Though recent data report the expression of various TLRs in the central nervous system, TLR expression patterns in the peripheral nervous system have not been determined yet. We observed that Schwann cells express relatively high levels of TLRs, with especially TLR3 and TLR4 being prominent. Sensory and motor neurons hardly express TLRs at all. Through the use of NF-κB signaling as read-out, we could show that all TLRs are functional in Schwann cells and that bacterial lipoprotein, a ligand for TLR1/TLR2 receptors yields the strongest response. In sciatic nerve, basal levels of TLRs closely reflect the expression patterns as determined in Schwann cells. TLR3, TLR4, and TLR7 are majorly expressed, pointing to their possible role in immune surveillance. Upon axotomy, TLR1 becomes strongly induced, while most other TLR expression levels remain unaffected. Altogether, our data suggest that similar to microglia in the brain, Schwann cells might act as sentinel cells in the PNS. Furthermore, acute neurodegeneration induces a shift in TLR expression pattern, most likely illustrating specialized functions of TLRs in basal versus
出处
《神经损伤与功能重建》
2010年第6期436-444,共9页
Neural Injury and Functional Reconstruction
