α-Lipoic acid enhances endogenous peroxisome-proliferator-activated receptor-γ to ameliorate experimental autoimmune encephalomyelitis in mice

Clin Sci (Lond). 2013 Oct;125(7):329-40. doi: 10.1042/CS20120560.

Abstract

ALA (α-lipoic acid) is a natural, endogenous antioxidant that acts as a PPAR-γ (peroxisome-proliferator-activated receptor-γ) agonist to counteract oxidative stress. Thus far, the antioxidative and immunomodulatory effects of ALA on EAE (experimental autoimmune encephalomyelitis) are not well understood. In this study, we found that ALA restricts the infiltration of inflammatory cells into the CNS (central nervous system) in MOG (myelin oligodendrocyte glycoprotein)-EAE mice, thus reducing the disease severity. In addition, we revealed that ALA significantly suppresses the number and percentage of encephalitogenic Th1 and Th17 cells and increases splenic Treg-cells (regulatory T-cells). Strikingly, we further demonstrated that ALA induces endogenous PPAR-γ centrally and peripherally but has no effect on HO-1 (haem oxygenase 1). Together, these data suggest that ALA can up-regulate endogenous systemic and central PPAR-γ and enhance systemic Treg-cells to inhibit the inflammatory response and ameliorate MOG-EAE. In conclusion, our data provide the first evidence that ALA can augment the production of PPAR-γ in vivo and modulate adaptive immunity both centrally and peripherally in EAE and may reveal further antioxidative and immunomodulatory mechanisms for the application of ALA in human MS (multiple sclerosis).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use*
  • Drug Evaluation, Preclinical / methods
  • Encephalomyelitis, Autoimmune, Experimental / drug therapy*
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Encephalomyelitis, Autoimmune, Experimental / metabolism
  • Heme Oxygenase-1 / biosynthesis
  • Heme Oxygenase-1 / drug effects
  • Immunosuppressive Agents / pharmacology
  • Immunosuppressive Agents / therapeutic use
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / immunology
  • Membrane Proteins / biosynthesis
  • Membrane Proteins / drug effects
  • Mice
  • Mice, Inbred C57BL
  • PPAR gamma / biosynthesis
  • PPAR gamma / drug effects*
  • Spleen / immunology
  • Spleen / transplantation
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / immunology
  • Th1 Cells / drug effects
  • Th1 Cells / immunology
  • Th17 Cells / drug effects
  • Th17 Cells / immunology
  • Thioctic Acid / pharmacology
  • Thioctic Acid / therapeutic use*
  • Up-Regulation / drug effects
  • Up-Regulation / immunology

Substances

  • Antioxidants
  • Immunosuppressive Agents
  • Membrane Proteins
  • PPAR gamma
  • Thioctic Acid
  • Heme Oxygenase-1
  • Hmox1 protein, mouse