Cannabidiol Modifies the Formation of NETs in Neutrophils of Psoriatic Patients

Int J Mol Sci. 2020 Sep 16;21(18):6795. doi: 10.3390/ijms21186795.

Abstract

Psoriasis is associated with increased production of reactive oxygen species which leads to oxidative stress. As antioxidants can provide protection, the aim of this study was to evaluate the effects of cannabidiol (CBD) on neutrophil extracellular trap (NET) formation in psoriatic and healthy neutrophils. Important markers of NETosis were measured in healthy and psoriatic neutrophils after incubation with CBD, lipopolysaccharide (LPS), and LPS + CBD). The percentage of neutrophils undergoing NETosis and the level of NETosis markers (cfDNA, MPO, elastase) were higher in the neutrophils and blood plasma of psoriatic patients, compared to controls. After LPS treatment, all of the markers of NETosis, except elastase, and p47 and citrullinated histones, were increased in samples from healthy subjects and psoriasis patients. CBD reduced the concentrations of NETosis markers. This led to a reduction in NETosis, which was more pronounced in psoriatic neutrophils and neutrophils treated with LPS in both psoriatic and healthy participants. These results suggest that psoriatic patients neutrophils are at a higher risk of NETosis both in vitro and in vivo. CBD reduces NETosis, mainly in psoriatic neutrophils, possibly due to its antioxidant properties. The anti-NET properties of CBD suggest the positive effect of CBD in the treatment of autoimmune diseases.

Keywords: NETs; cannabidiol treatment; immunity; neutrophil traps; psoriasis.

MeSH terms

  • Adult
  • Cannabidiol / pharmacology*
  • Case-Control Studies
  • Cell-Free Nucleic Acids / analysis
  • Culture Media, Conditioned / chemistry
  • Drug Synergism
  • Enzyme Induction / drug effects
  • Extracellular Traps / drug effects*
  • Female
  • Humans
  • Lipopolysaccharides / pharmacology
  • Male
  • NADPH Oxidases / biosynthesis
  • NADPH Oxidases / physiology
  • Neutrophils / drug effects*
  • Oxidation-Reduction
  • Peroxidase / analysis
  • Psoriasis / blood
  • Psoriasis / immunology*
  • Reactive Oxygen Species / metabolism

Substances

  • Cell-Free Nucleic Acids
  • Culture Media, Conditioned
  • Lipopolysaccharides
  • Reactive Oxygen Species
  • Cannabidiol
  • MPO protein, human
  • Peroxidase
  • NADPH Oxidases
  • neutrophil cytosolic factor 1