title: FAAH-mediated modulation of TLR3-induced neuroinflammation in the rat hippocampus.
abstract: The present study examined the effect of enhancing fatty acid amide hydrolase (FAAH) substrate levels in vivo on Toll-like receptor (TLR)3-induced neuroinflammation. Systemic and central (i.c.v.) administration of the FAAH inhibitor URB597 increased hippocampal levels of the N-acylethanolamines palmitoylethanolamide and oleoylethanolamide, but not anandamide. Systemic URB597 increased IFNα, IFNγ and IL-6 expression following TLR3 activation and attenuated TLR3-induced IL-1β and TNFα expression. In comparison, central URB597 administration attenuated the TLR3-induced increase in TNFα and IFNγ expression (and associated downstream genes IP-10 and SOCS1), while concurrently increasing IL-10 expression. These data support an important role for FAAH-mediated regulation of TLR3-induced neuroinflammatory responses.
authors.affiliation: Physiology, School of Medicine, National University of Ireland, Galway, Ireland; NCBES Centre for Pain Research and Neuroscience Centre, National University of Ireland, Galway, Ireland.
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Henry
authors.affiliation: Physiology, School of Medicine, National University of Ireland, Galway, Ireland; Pharmacology and Therapeutics, School of Medicine, National University of Ireland, Galway, Ireland; NCBES Centre for Pain Research and Neuroscience Centre, National University of Ireland, Galway, Ireland.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Kerr
authors.affiliation: Pharmacology and Therapeutics, School of Medicine, National University of Ireland, Galway, Ireland; NCBES Centre for Pain Research and Neuroscience Centre, National University of Ireland, Galway, Ireland.
authors.forename: David P
authors.initials: DP
authors.lastname: Finn
authors.affiliation: Physiology, School of Medicine, National University of Ireland, Galway, Ireland; NCBES Centre for Pain Research and Neuroscience Centre, National University of Ireland, Galway, Ireland. Electronic address: Michelle.roche@nuigalway.ie.
authors.forename: Michelle
authors.initials: M
authors.lastname: Roche
mesh_terms: D000581:Amidohydrolases / Q000378:metabolism*; D000818:Animals; D001549:Benzamides / Q000008:administration & dosage; D002219:Carbamates / Q000008:administration & dosage; D002853:Chromatography, Liquid; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004333:Drug Administration Routes; D004660:Encephalitis / Q000139:chemically induced* / Q000473:pathology*; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D007369:Interferon Inducers / Q000633:toxicity; D008297:Male; D011070:Poly I-C / Q000633:toxicity; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry; D051196:Toll-Like Receptor 3 / Q000378:metabolism*; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D001549:Benzamides; D002219:Carbamates; D016207:Cytokines; D004791:Enzyme Inhibitors; D007369:Interferon Inducers; D011070:Poly I-C; D012333:RNA, Messenger; D051196:Toll-Like Receptor 3; D000099252:Fatty Acid Amide Hydrolases; C530472:TLR3 protein, rat; C500528:cyclohexyl carbamic acid 3'-carbamoylbiphenyl-3-yl ester
keywords: Anandamide; Cannabinoid; Cytokine; Fatty acid amide hydrolase; Interferon; Virus