LIPOPOLYSACCHARIDE DIFFERENTIALLY MODULATES EXPRESSION OF CYTOKINES AND CYCLOOXYGENASES IN DORSAL ROOT GANGLION CELLS VIA TOLL-LIKE RECEPTOR-4 DEPENDENT PATHWAYS
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AbstractWe have examined the functional expression of Toll-like receptor 4 (TLR4) in adult male rat dorsal root ganglion (DRG) cells in culture by studying changes in pro-inflammatory cytokines and cyclooxygenase (COX)-dependent prostanoid production. In the mixed population of DRG neurons and glial cells, only DRG neurons expressed cell surface TLR4 along with MD-2 and CD14. This classical TLR4 signaling complex on DRG neurons responded to lipopolysaccharide (LPS) with a TLR4-dependent and time-dependent increase in interleukin-1 beta and tumor necrosis factor-alpha mRNA expression which was entirely dependent on NF-kappa B activity. In contrast, after 2-h incubation with DRG cells, LPS-stimulated COX-2 was regulated by both NF-kappa B and transactivation of epidermal growth factor receptor (EGFR) with potential downstream activation of ERK1/2 and p38 kinase. In contrast to this evidence for myeloid differentiation primary response gene-88 (MyD88)-dependent signaling, no evidence was obtained for TIR-domain-containing adaptor-inducing interferon-beta (TRIF)-dependent signaling from TLR4 in DRG neurons. LPS surprisingly produced a time-dependent decrease in COX-1 protein which likely facilitates the COX-2-dependent production of prostaglandin E-2 and prostacyclin. Our study is the first to demonstrate the activation of TLR4-dependent production of prostaglandin E-2 and prostacyclin in DRG cell cultures. Our findings support the concept that the activation of TLR4 on primary sensory neurons by endogenous ligands may underlie neuropathic and inflammatory pain states. (C) 2014 IBRO. Published by Elsevier Ltd. All rights reserved.
All Author(s) ListTse KH, Chow KBS, Leung WK, Wong YH, Wise H
Journal nameNeuroscience
Year2014
Month5
Day16
Volume Number267
PublisherPERGAMON-ELSEVIER SCIENCE LTD
Pages241 - 251
ISSN0306-4522
eISSN1873-7544
LanguagesEnglish-United Kingdom
Keywordscell signaling; dorsal root ganglia; lipopolysaccharide; neuroinflammation; Toll-like receptor-4
Web of Science Subject CategoriesNeurosciences; NEUROSCIENCES; Neurosciences & Neurology

Last updated on 2020-08-07 at 04:34