Immunomodulatory properties of increased levels of liver X receptor beta in peripheral blood mononuclear cells from multiple sclerosis patients

Exp Neurol. 2007 Apr;204(2):759-66. doi: 10.1016/j.expneurol.2007.01.013. Epub 2007 Jan 24.

Abstract

Liver X receptors (LXRalpha and LXRbeta) are nuclear transcription factors that inhibit transcription of genes of inflammation while inducing HMGCoA reductase. In this paper we demonstrate increased mRNA levels of LXRbeta in peripheral blood mononuclear cells (PBMCs) from multiple sclerosis patients with respect to other neurological patients and healthy controls (HC) (p<0.01). Agonist-induced activation of LXRs partially counteracts the anti-CD3+ anti-CD28-induced proliferation of T cells (p<0.01) and secretion of IFNgamma (p<0.001) from PBMCs of MS patients as well as of HC. Secretion of IL-4 is not affected. Our findings suggest that regulation of cholesterol metabolism not strictly related to inhibition of HMGCoA reductase can modulate activity of lymphocytes in MS.

MeSH terms

  • ATP Binding Cassette Transporter 1
  • ATP-Binding Cassette Transporters / metabolism
  • Adolescent
  • Adult
  • Analysis of Variance
  • Antigens, CD / metabolism
  • Cell Proliferation / drug effects
  • DNA-Binding Proteins / agonists
  • DNA-Binding Proteins / metabolism*
  • Enzyme Activation / drug effects
  • Female
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / physiology*
  • Humans
  • Hydrocarbons, Fluorinated
  • Hydroxymethylglutaryl CoA Reductases / metabolism
  • Interferon-gamma / metabolism
  • Leukocytes / drug effects
  • Leukocytes / metabolism*
  • Liver X Receptors
  • Male
  • Middle Aged
  • Multiple Sclerosis / pathology*
  • Orphan Nuclear Receptors
  • RNA, Messenger / metabolism
  • Receptors, Cytoplasmic and Nuclear / agonists
  • Receptors, Cytoplasmic and Nuclear / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Statistics, Nonparametric
  • Sulfonamides / pharmacology
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / physiology

Substances

  • ATP Binding Cassette Transporter 1
  • ATP-Binding Cassette Transporters
  • Antigens, CD
  • DNA-Binding Proteins
  • Hydrocarbons, Fluorinated
  • Liver X Receptors
  • NR1H3 protein, human
  • Orphan Nuclear Receptors
  • RNA, Messenger
  • Receptors, Cytoplasmic and Nuclear
  • Sulfonamides
  • T0901317
  • Interferon-gamma
  • Hydroxymethylglutaryl CoA Reductases