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Bacterial lipopolysaccharide regulates nociceptin expression in sensory neurons
Author(s) -
Acosta Cristian,
Davies Alun
Publication year - 2008
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.21565
Subject(s) - nociceptin receptor , tlr4 , dorsal root ganglion , receptor , lipopolysaccharide , microbiology and biotechnology , proinflammatory cytokine , chemistry , sensory neuron , opioid receptor , sensory system , inflammation , opioid , biology , neuroscience , immunology , opioid peptide , biochemistry
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 LPS, 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. © 2007 Wiley‐Liss, Inc.