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

J Neuroimmunol. 2014 Feb 15;267(1-2):61-72. doi: 10.1016/j.jneuroim.2013.12.008. Epub 2013 Dec 12.

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.

Keywords: Cannabinoid; Cytokine; Huntington's disease; NF-κB p65/RelA; Neuroinflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Amidohydrolases / genetics
  • Amidohydrolases / metabolism
  • Animals
  • Arachidonic Acids / pharmacology
  • Cannabinoids / pharmacology
  • Cells, Cultured
  • Corpus Striatum / cytology
  • Corpus Striatum / metabolism*
  • Cytokines / genetics
  • Cytokines / metabolism*
  • Disease Models, Animal
  • Endocannabinoids / agonists
  • Endocannabinoids / antagonists & inhibitors
  • Endocannabinoids / metabolism*
  • Enzyme Inhibitors / pharmacology
  • Female
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology
  • Humans
  • Huntingtin Protein
  • Huntington Disease / pathology*
  • Indoles / pharmacology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Middle Aged
  • NF-kappa B / genetics
  • NF-kappa B / metabolism*
  • Nerve Tissue Proteins / genetics
  • Neurons / drug effects
  • Neurons / metabolism
  • Nuclear Proteins / genetics
  • Receptor, Cannabinoid, CB1 / genetics
  • Receptor, Cannabinoid, CB1 / metabolism
  • Transcription Factor RelA / genetics
  • Transcription Factor RelA / metabolism*
  • Trinucleotide Repeats / genetics
  • Young Adult

Substances

  • Arachidonic Acids
  • Cannabinoids
  • Cytokines
  • Endocannabinoids
  • Enzyme Inhibitors
  • Htt protein, mouse
  • Huntingtin Protein
  • Indoles
  • NF-kappa B
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • Receptor, Cannabinoid, CB1
  • Transcription Factor RelA
  • arachidonyl-2-chloroethylamide
  • HU 308
  • Amidohydrolases
  • fatty-acid amide hydrolase
  • iodopravadoline