THE EXPRESSION OF TOLL-LIKE RECEPTOR 4, 7 AND CO-RECEPTORS IN NEUROCHEMICAL SUB-POPULATIONS OF RAT TRIGEMINAL GANGLION SENSORY NEURONS
THE EXPRESSION OF TOLL-LIKE RECEPTOR 4, 7 AND CO-RECEPTORS IN NEUROCHEMICAL SUB-POPULATIONS OF RAT TRIGEMINAL GANGLION SENSORY NEURONS
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DOI：
10.1016/j.neuroscience.2015.09.069
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发表时间：
2015-12-03
期刊：
影响因子：
3.3
通讯作者：
Thompson, S. W. N.
中科院分区：
文献类型：
--
作者：
Helley, M. P.;Abate, W.;Thompson, S. W. N.
最近发现哺乳动物伤害感受器表达Toll样受体（TLR），这提高了这些细胞直接检测和响应病原体的可能性，其暗示直接伤害感受器激活或致敏。已经鉴定了一系列神经元TLR，然而缺乏关于这些受体在感觉神经元亚群内的表达分布的详细描述。关于感觉神经元上TLR4受体复合物的组成也有一些争论。在这里，我们使用了一系列的技术来量化表达的TLR4，TLR7和一些相关的分子内的神经化学鉴定的亚群三叉神经（TG）和背根（DRG）神经节感觉神经元。我们还详细的表达模式和共表达的两种亚型的溶血磷脂酰胆碱酰基转移酶（LPCAT），磷脂重塑酶先前被证明参与单核细胞的脂多糖依赖性TLR4反应，在感觉神经节内。免疫组织化学显示，TLR4和TLR7优先与TG和DRG内的伤害感受器群体的标记物瞬时受体电位类谷蛋白1（TRPV1）和嘌呤能受体P2X配体门控离子通道3（P2X3）共定位。基因表达谱显示，TG感觉神经元表达一系列TLR相关分子。LPCAT 1由一定比例的伤害感受器和非伤害感受神经元表达。LPCAT 2免疫染色在TG和DRG内的神经元分布中不存在，并且仅限于幼稚条件下的非神经元细胞类型。总之，我们的研究结果表明，伤害感受器表达的分子机制需要直接响应病原体的挑战，独立于先天免疫系统。(C)2015年IBRO。由爱思唯尔有限公司出版。保留所有权利。
The recent discovery that mammalian nociceptors express Toll-like receptors (TLRs) has raised the possibility that these cells directly detect and respond to pathogens with implications for either direct nociceptor activation or sensitization. A range of neuronal TLRs have been identified, however a detailed description regarding the distribution of expression of these receptors within sub-populations of sensory neurons is lacking. There is also some debate as to the composition of the TLR4 receptor complex on sensory neurons. Here we use a range of techniques to quantify the expression of TLR4, TLR7 and some associated molecules within neurochemically-identified sub-populations of trigeminal (TG) and dorsal root (DRG) ganglion sensory neurons. We also detail the pattern of expression and co-expression of two isoforms of lysophosphatidylcholine acyltransferase (LPCAT), a phospholipid remodeling enzyme previously shown to be involved in the lipopolysaccharide-dependent TLR4 response in monocytes, within sensory ganglia. Immunohistochemistry shows that both TLR4 and TLR7 preferentially co-localize with transient receptor potential vallinoid 1 (TRPV1) and purinergic receptor P2X ligand-gated ion channel 3 (P2X3), markers of nociceptor populations, within both TG and DRG. A gene expression profile shows that TG sensory neurons express a range of TLR-associated molecules. LPCAT1 is expressed by a proportion of both nociceptors and non-nociceptive neurons. LPCAT2 immunostaining is absent from neuronal profiles within both TG and DRG and is confined to non-neuronal cell types under naive conditions. Together, our results show that nociceptors express the molecular machinery required to directly respond to pathogenic challenge independently from the innate immune system. (C) 2015 IBRO. Published by Elsevier Ltd. All rights reserved.