The relevance of ceramides and their synthesizing enzymes for multiple sclerosis

Clin Sci (Lond). 2018 Aug 17;132(17):1963-1976. doi: 10.1042/CS20180506. Print 2018 Sep 14.


Ceramide synthases (CerS) synthesize chain length specific ceramides (Cer), which mediate cellular processes in a chain length-dependent manner. In experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS), we observed that the genetic deletion of CerS2 suppresses EAE pathology by interaction with granulocyte-colony stimulating factor (G-CSF) signaling and CXC motif chemokine receptor 2 (CXCR2) expression, leading to impaired neutrophil migration. In the present study, we investigated the importance of Cers and their synthesizing/metabolizing enzymes in MS. For this purpose, a longitudinal study with 72 MS patients and 25 healthy volunteers was performed. Blood samples were collected from healthy controls and MS patients over 1- or 3-year periods, respectively. Immune cells were counted using flow cytometry, ceramide levels were determined using liquid chromatography-tandem mass spectrometry, and mRNA expression was analyzed using quantitative PCR. In white blood cells, C16-LacCer and C24-Cer were down-regulated in MS patients in comparison with healthy controls. In plasma, C16-Cer, C24:1-Cer, C16-GluCer, and C24:1-GluCer were up-regulated and C16-LacCer was down-regulated in MS patients in comparison with healthy controls. Blood samples from MS patients were characterized by an increased B-cell number. However, there was no correlation between B-cell number and Cer levels. mRNA expression of Cer metabolizing enzymes and G-CSF signaling enzymes was significantly increased in MS patients. Interestingly, G-CSF receptor (G-CSFR) and CXCR2 mRNA expression correlated with CerS2 and UDP-glucose Cer glucosyltransferase (UGCG) mRNA expression. In conclusion, our results indicate that Cer metabolism is linked to G-CSF signaling in MS.

Keywords: CXCR2; Ceramide synthase 2; Granulocyte-colony stimulating factor; UDP-glucose ceramide glucosyltransferase; ceramide synthase 6; multiple sclerosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • B-Lymphocytes / metabolism
  • Ceramides / blood*
  • Ceramides / chemistry
  • Ceramides / metabolism
  • Gene Expression / drug effects
  • Granulocyte Colony-Stimulating Factor / metabolism
  • Granulocyte Colony-Stimulating Factor / pharmacology
  • Humans
  • Leukocyte Count
  • Leukocytes / metabolism
  • Longitudinal Studies
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Monosaccharide Transport Proteins / genetics
  • Monosaccharide Transport Proteins / metabolism
  • Multiple Sclerosis / blood*
  • Multiple Sclerosis / genetics
  • Multiple Sclerosis / metabolism*
  • Receptors, Granulocyte Colony-Stimulating Factor / genetics
  • Receptors, Granulocyte Colony-Stimulating Factor / metabolism
  • Receptors, Interleukin-8B / genetics
  • Receptors, Interleukin-8B / metabolism
  • Signal Transduction
  • Sphingosine N-Acyltransferase / genetics
  • Sphingosine N-Acyltransferase / metabolism*
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*


  • Ceramides
  • Membrane Proteins
  • Monosaccharide Transport Proteins
  • Receptors, Granulocyte Colony-Stimulating Factor
  • Receptors, Interleukin-8B
  • Tumor Suppressor Proteins
  • UDP-galactose translocator
  • Granulocyte Colony-Stimulating Factor
  • CERS2 protein, human
  • Sphingosine N-Acyltransferase