title: The cytokine and endocannabinoid systems are co-regulated by NF-κB p65/RelA in cell culture and transgenic mouse models of Huntington's disease and in striatal tissue from Huntington's disease patients.
abstract: Transcriptional dysregulation is a major pathological feature of Huntington's disease (HD). The goal of this study was to understand how p65/RelA co-regulated genes, specifically those of the cytokine and endocannabinoid systems, were affected in HD. p65/RelA levels were lower in human HD tissue and R6/2 HD mice, as were the levels of the type 1 cannabinoid receptor (CB1), IL-1β, IL-8, CCL5, GM-CSF, MIP-1β, and TNFα, all of which may be regulated by p65/RelA. Activation of p65/RelA restored CB1 and CCL5 expression in STHdh cell models of HD. Therefore, p65/RelA activation may normalize the expression of some genes in HD.
authors.affiliation: Department of Pharmacology, Dalhousie University, 6th Fl. Sir Charles Tupper Medical Bldg, 5850 College St, Halifax, NS B3H 4R2, Canada. Electronic address: robert.laprairie@da.ca.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Laprairie
authors.affiliation: Department of Pathology, Dalhousie University, 11th Fl. Sir Charles Tupper Medical Bldg, 5850 College St, Halifax, NS B3H 4R2, Canada. Electronic address: jordan.warford@dal.ca.
authors.forename: Jordan R
authors.initials: JR
authors.lastname: Warford
authors.affiliation: Department of Physiology, University of Toronto, Medical Sciences Bldg, 1 King's College Circle, Toronto, ON M5S 1A8, Canada. Electronic address: sarah.hutchings@mail.utoronto.ca.
authors.forename: Sarah
authors.initials: S
authors.lastname: Hutchings
authors.affiliation: Department of Pharmacology, Dalhousie University, 6th Fl. Sir Charles Tupper Medical Bldg, 5850 College St, Halifax, NS B3H 4R2, Canada. Electronic address: george.robertson@dal.ca.
authors.forename: George S
authors.initials: GS
authors.lastname: Robertson
authors.affiliation: Department of Pharmacology, Dalhousie University, 6th Fl. Sir Charles Tupper Medical Bldg, 5850 College St, Halifax, NS B3H 4R2, Canada. Electronic address: melanie.kelly@dal.ca.
authors.forename: Melanie E M
authors.initials: ME
authors.lastname: Kelly
authors.affiliation: Department of Pharmacology, Dalhousie University, 6th Fl. Sir Charles Tupper Medical Bldg, 5850 College St, Halifax, NS B3H 4R2, Canada. Electronic address: emdenova@dal.ca.
authors.forename: Eileen M
authors.initials: EM
authors.lastname: Denovan-Wright
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000581:Amidohydrolases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D002186:Cannabinoids / Q000494:pharmacology; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000166:cytology / Q000378:metabolism*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D063388:Endocannabinoids / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000473:pathology*; D007211:Indoles / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008875:Middle Aged; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics; D043884:Receptor, Cannabinoid, CB1 / Q000235:genetics / Q000378:metabolism; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism*; D018911:Trinucleotide Repeats / Q000235:genetics; D055815:Young Adult; D000099252:Fatty Acid Amide Hydrolases
chemical_list: D000581:Amidohydrolases; D001095:Arachidonic Acids; D002186:Cannabinoids; D016207:Cytokines; D063388:Endocannabinoids; D004791:Enzyme Inhibitors; D000071058:Huntingtin Protein; D007211:Indoles; D016328:NF-kappa B; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D043884:Receptor, Cannabinoid, CB1; D051996:Transcription Factor RelA; D000099252:Fatty Acid Amide Hydrolases; C506812:Htt protein, mouse; C119325:arachidonyl-2-chloroethylamide; C402416:HU 308; C094023:iodopravadoline
keywords: Cannabinoid; Cytokine; Huntington's disease; NF-κB p65/RelA; Neuroinflammation