ROCK inhibitor abolishes the antibody response in experimental autoimmune myasthenia gravis

Mol Cell Neurosci. 2016 Jul:74:106-13. doi: 10.1016/j.mcn.2016.05.001. Epub 2016 May 7.

Abstract

The Rho/Rho kinase (ROCK) pathway serves as molecular switches in many biological processes including the immune response. ROCK inhibitors lead to amelioration of some autoimmune diseases. The present study was designed to define whether a selective ROCK inhibitor, fasudil, was effective in experimental autoimmune myasthenia gravis (EAMG) and investigate the underlying mechanisms. Here we found fasudil effectively attenuated the development of ongoing EAMG. Fasudil abolished the antibody production and function by decreasing follicular helper T cells and CD19(+) B cells, especially germinal center B cells. Moreover, fasudil reduced the expression of CD80 on lymph node mononuclear cells. These findings suggest the inhibition of ROCK might be a potential therapeutic strategy for antibody-mediated autoimmune diseases.

Keywords: Antibody; Experimental autoimmune myasthenia gravis; Follicular helper T cells; Germinal center; Rho kinase inhibitor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / analogs & derivatives*
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / pharmacology
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / therapeutic use
  • Animals
  • Autoimmunity / drug effects
  • B-Lymphocytes / drug effects
  • B-Lymphocytes / immunology
  • Female
  • Germinal Center / cytology
  • Germinal Center / drug effects
  • Myasthenia Gravis, Autoimmune, Experimental / therapy*
  • Protein Kinase Inhibitors / pharmacology*
  • Protein Kinase Inhibitors / therapeutic use
  • Rats
  • Rats, Inbred Lew
  • T-Lymphocytes, Helper-Inducer / drug effects
  • T-Lymphocytes, Helper-Inducer / immunology
  • rho-Associated Kinases / antagonists & inhibitors*

Substances

  • Protein Kinase Inhibitors
  • 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine
  • rho-Associated Kinases
  • fasudil