Bacterial lipopolysaccharide regulates nociceptin expression in sensory neurons
Bacterial lipopolysaccharide regulates nociceptin expression in sensory neurons
复制标题
DOI：
10.1002/jnr.21565
复制
发表时间：
2008-04-01
影响因子：
4.2
通讯作者：
Davies, Alun
中科院分区：
文献类型：
--
作者：
Acosta, Cristian;Davies, Alun
孤啡肽/孤啡肽FQ（N/OFQ）是一种阿片样物质相关的肽，在外周炎症后在体内感觉神经元中显著上调，并且在疼痛生理学中起关键作用。为了确定物质，上调N/OFQ表达的感觉神经元，我们进行了体外筛选，使用纯化的成年小鼠背根神经节（DRG）神经元，并确定了有效的促炎剂细菌脂多糖（LPS）作为一个非常有效的诱导剂N/OFQ。这些神经元对LPS的强烈反应使我们能够识别出一个假定的神经元LPS受体复合物的组成部分。与免疫系统相反，其中功能性LPS受体复合物由CD-14连同髓样细胞上的MD-2和TLR 4或成熟B细胞上的同源受体MD-1和RP 105组成，DRG神经元表达CD-14、TLR 4和MD-1的不寻常组合。针对TLR 4和MD-1的阻断抗体阻止了由LIPS诱导的N/OFQ，并且在免疫沉淀实验中，MD-1与TLR 4共沉淀。我们的研究结果表明，LPS调节N/OFN的表达在感觉神经元通过一种新的组合LPS受体成分，并首次证明了一个直接的行动的先天免疫反应的关键启动神经元。(C)2007 Wiley-Liss，Inc.
Nociceptin/orphanin FQ (N/OFQ) is an opioid-related peptide that is markedly up-regulated in sensory neurons in vivo following peripheral inflammation and plays a key role in pain physiology. To identify substances that up-regulate N/OFQ expression in sensory neurons, we carried out an in vitro screen using purified adult mouse dorsal root ganglion (DRG) neurons and identified the potent proinflammatory agent bacterial lipopolysaccharide (LPS) as a very effective inducer of N/OFQ. The robust response of these neurons to LPS enabled us to identify the components of a putative neuronal LPS receptor complex. In contrast to the immune system, where the functional LPS receptor complex is composed of CD-14 together with either MD-2 and TLR4 on myeloid cells or the homologous receptors MD-1 and RP105 on mature B cells, DRG neurons express the unusual combination of CD-14, TLR4, and MD-1. Blocking antibodies against TLR4 and MD-1 prevented induction of N/OFQ by LIPS, and, in immunoprecipitation experiments, MD-1 coprecipitated with TLR4. Our findings suggest that LPS regulates N/OFN expression in sensory neurons via a novel combination of LPS receptor components and demonstrate for the first time a direct action of a key initiator of innate immune responses on neurons. (C) 2007 Wiley-Liss, Inc.