Effect of fingolimod action on the release of monocyte-derived microvesicles in multiple sclerosis patients

J Neuroimmunol. 2018 Oct 15:323:43-48. doi: 10.1016/j.jneuroim.2018.07.008. Epub 2018 Jul 17.

Abstract

Recently, microvesicles (MVs) were considered as important mediators of intercellular communication, especially in pathological conditions as Multiple Sclerosis (MS). In myeloid cells, MV shedding is induced by the receptor P2X7 with the involvement of acid sphingomyelinase (A-SMase) and release of the IL-1β. In this study we evaluate how Fingolimod affects MVs production by the monocytes, as well as P2X7R, IL-1β expression and A-SMase activity. Treatment decreased MVs production and IL-1β expression. This effect was associated with the inhibition of A-SMase activity in BzATP-stimulated monocytes from MS patients. These evidences suggest monocyte MVs as a possible disease and drug-efficacy biomarkers.

Keywords: Acid sphingomyelinase; Fingolimod; IL-1β; Microvesicles; Multiple sclerosis; P2X7 receptor.

MeSH terms

  • Adult
  • Cell-Derived Microparticles / drug effects
  • Cell-Derived Microparticles / metabolism*
  • Female
  • Fingolimod Hydrochloride / pharmacology
  • Fingolimod Hydrochloride / therapeutic use*
  • Humans
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / metabolism
  • Male
  • Monocytes / drug effects
  • Monocytes / metabolism*
  • Multiple Sclerosis / drug therapy*
  • Multiple Sclerosis / metabolism*

Substances

  • Fingolimod Hydrochloride