Matrine ameliorates experimental autoimmune encephalomyelitis by modulating chemokines and their receptors

Exp Mol Pathol. 2015 Oct;99(2):212-9. doi: 10.1016/j.yexmp.2015.06.008. Epub 2015 Jun 18.

Abstract

Multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), are autoimmune diseases characterized by immune-mediated neuroinflammation, demyelination and neurodegeneration of the central nervous system (CNS). While matrine (MAT), a monomer that is used in traditional Chinese medicine as an anti-inflammatory treatment, delayed onset and ameliorated severity of EAE, the underlying mechanisms have not been fully elucidated. In this study, we investigated the relationship between the clinical effect of MAT and the levels of certain important chemokines/chemokine receptors. Our results showed that attenuated severity of EAE resulting from MAT treatment was positively correlated with the reduction of CCL2 and CXCL10 levels in the periphery and the CNS; both of these chemokines play a crucial role in the recruitment and accumulation of inflammatory cells, especially monocytes/macrophages and T cells, into the CNS. The levels of their corresponding receptors, CCR2 and CXCR3, were also significantly reduced after MAT treatment. Taken together, our data indicate that MAT may be an effective immunomodulatory therapeutic approach for MS/EAE by countering the immune cell recruitment mechanisms.

Keywords: CCL2/CCR2; CXCL10/CXCR3; Chemokine/chemokine receptor; EAE/MS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / pharmacology*
  • Animals
  • Chemokines / genetics
  • Chemokines / metabolism*
  • Encephalomyelitis, Autoimmune, Experimental / drug therapy*
  • Encephalomyelitis, Autoimmune, Experimental / genetics
  • Encephalomyelitis, Autoimmune, Experimental / metabolism*
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Gene Expression Regulation / drug effects*
  • Immunoenzyme Techniques
  • Matrines
  • Quinolizines / pharmacology*
  • RNA, Messenger / genetics
  • Rats
  • Rats, Wistar
  • Real-Time Polymerase Chain Reaction
  • Receptors, Chemokine / genetics
  • Receptors, Chemokine / metabolism*
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Alkaloids
  • Chemokines
  • Quinolizines
  • RNA, Messenger
  • Receptors, Chemokine
  • Matrines