Methylene blue alleviates experimental autoimmune encephalomyelitis by modulating AMPK/SIRT1 signaling pathway and Th17/Treg immune response

J Neuroimmunol. 2016 Oct 15:299:45-52. doi: 10.1016/j.jneuroim.2016.08.014. Epub 2016 Aug 16.

Abstract

Methylene blue (MB) is an effective neuroprotectant in many neurological disorders. AMP-activated protein kinase (AMPK)/silent mating-type information regulation 2 homolog 1 (SIRT1) plays a crucial role in maintaining inflammatory responses and shows a synergistic effect on cell homeostasis. We investigated the effect of MB on experimental autoimmune encephalomyelitis (EAE), a classical animal model of multiple sclerosis (MS). MB treatment reduced the clinical scores of EAE significantly and attenuated pathological injuries in spinal cords. Furthermore, the protective effects of MB were related to the activation of AMPK/SIRT1 signaling pathway. In addition, MB treatment alleviated T helper type17 (Th17) responses and increased regulatory T cell (Treg) responses. Our findings suggest that MB could be a promising reagent to treat autoimmune diseases and MS.

Keywords: AMPK/SIRT1; Experimental autoimmune encephalomyelitis; Methylene blue; Multiple sclerosis; Th17; Treg.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • AMP-Activated Protein Kinases / metabolism*
  • Animals
  • Cells, Cultured
  • Encephalomyelitis, Autoimmune, Experimental / drug therapy
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Encephalomyelitis, Autoimmune, Experimental / metabolism*
  • Female
  • Immunity, Cellular / drug effects*
  • Immunity, Cellular / immunology
  • Methylene Blue / pharmacology
  • Methylene Blue / therapeutic use*
  • Mice
  • Mice, Inbred C57BL
  • Signal Transduction / drug effects
  • Signal Transduction / immunology
  • Sirtuin 1 / immunology
  • Sirtuin 1 / metabolism*
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism*
  • Th17 Cells / drug effects
  • Th17 Cells / immunology
  • Th17 Cells / metabolism*

Substances

  • AMP-Activated Protein Kinases
  • Sirt1 protein, mouse
  • Sirtuin 1
  • Methylene Blue