Genistein modulates the expression of Toll-like receptors in experimental autoimmune encephalomyelitis

Inflamm Res. 2018 Jul;67(7):597-608. doi: 10.1007/s00011-018-1146-7. Epub 2018 Apr 23.

Abstract

Objective and design: The present work investigates the modulation of experimental autoimmune encephalomyelitis (EAE) using genistein before the EAE induction.

Material: Female C57BL/6 mice (n = 96 mice/experiment), 4-6 weeks old, were used to induce the EAE. The mice were divided into three experimental groups: non-immunized group, immunized group (EAE), and immunized and treated with genistein group (Genistein).

Treatment: Genistein was used at a dose of 200 mg/kg s.c. and were initiated 2 days before the immunization and continued daily until day 6 postimmunization.

Methods: Animals were monitored daily for clinical signs of EAE up to day 21. Inflammatory infiltration, demyelination, Toll-like receptor (TLR) expression, cytokines and transcription factors were analyzed in spinal cords.

Results: The present study demonstrates, for the first time, the genistein ability to modulate the factors involved in the innate immune response in the early stages of EAE. The genistein therapy delayed the onset of the disease, with reduced inflammatory infiltration and demyelination. In addition, the expression of TLR3, TLR9 and IFN-β were increased in genistein group, with reduction in the factors of TH1 and Th17 cells.

Conclusion: These findings shed light on the potential of genistein as a prophylactic strategy for multiple sclerosis (MS) prevention.

Keywords: Experimental autoimmune encephalomyelitis; IFN-β; Immune response; Multiple sclerosis; Toll-like.

MeSH terms

  • Animals
  • Cytokines / genetics
  • Cytokines / immunology
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Encephalomyelitis, Autoimmune, Experimental / prevention & control
  • Female
  • Genistein / pharmacology*
  • Genistein / therapeutic use*
  • Immunologic Factors / pharmacology*
  • Immunologic Factors / therapeutic use*
  • Macrophages / drug effects
  • Macrophages / immunology
  • Mice, Inbred C57BL
  • Multiple Sclerosis / prevention & control
  • Myelin Sheath / drug effects
  • Spinal Cord / drug effects
  • Spinal Cord / immunology
  • Spinal Cord / pathology
  • Toll-Like Receptors / immunology*

Substances

  • Cytokines
  • Immunologic Factors
  • Toll-Like Receptors
  • Genistein