title: PGE2 released by primary sensory neurons modulates Toll-like receptor 4 activities through an EP4 receptor-dependent process.
abstract: Exogenous prostaglandin E2 (PGE2) displays mixed regulatory properties with regard to inflammatory gene expression in dorsal root ganglion (DRG) cells. We show here that endogenously-produced nanomolar concentrations of PGE2, such as that generated in response to Toll-like receptor 4 (TLR4) stimulation, inhibits both cyclooxygenase-2 (COX-2) and tumour necrosis factor alpha (TNFα) mRNA expression in DRG cells in an EP4 receptor-dependent manner. DRG neurons appear to be the major source of PGE2 in the DRG and likely serve as both an autocrine and paracrine system for limiting over-activation of both DRG neurons and glial cells in response to TLR4 stimulation.
authors.affiliation: School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China. Electronic address: frankitse@ust.hk.
authors.forename: Kai-Hei
authors.initials: KH
authors.lastname: Tse
authors.affiliation: School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.
authors.forename: Kevin B S
authors.initials: KBS
authors.lastname: Chow
authors.affiliation: School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region, China.
authors.forename: Helen
authors.initials: H
authors.lastname: Wise
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000166:cytology; D005786:Gene Expression Regulation / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D011804:Quinolines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D058309:Receptors, Prostaglandin E, EP4 Subtype / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000378:metabolism*; D013449:Sulfonamides / Q000494:pharmacology; D013876:Thiophenes / Q000494:pharmacology; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D014230:Triazoles / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D017077:Culture Media, Conditioned; D004791:Enzyme Inhibitors; D005904:Glial Fibrillary Acidic Protein; C508711:L-161982; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; C528911:N-((4-(5,9-diethoxy-6-oxo-6,8-dihydro-7H-pyrrolo(3,4-g)quinolin-7-yl)-3-methylbenzyl)sulfonyl)-2-(2-methoxyphenyl)acetamide; D011804:Quinolines; D058309:Receptors, Prostaglandin E, EP4 Subtype; D013449:Sulfonamides; D013876:Thiophenes; D051197:Toll-Like Receptor 4; D014230:Triazoles; D014409:Tumor Necrosis Factor-alpha; D000242:Cyclic AMP; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat; D017868:Cyclic AMP-Dependent Protein Kinases; D015232:Dinoprostone
keywords: Dorsal root ganglia; EP(4); PGE(2); Primary sensory neurons; Toll-like receptor 4