2016
DOI: 10.3389/fphar.2016.00412
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Interferon-Beta Increases Plasma Ceramides of Specific Chain Length in Multiple Sclerosis Patients, Unlike Fingolimod or Natalizumab

Abstract: Fingolimod is used for the treatment of multiple sclerosis (MS) and targets receptors for the bioactive sphingolipid sphingosine-1-phosphate (S1P). Whether fingolimod or other MS therapies conversely affect plasma concentrations of sphingolipids has, however, not yet been analyzed. Herein, we quantified 15 representative sphingolipid species by mass spectrometry in plasma from relapsing-remitting MS patients currently under fingolimod (n = 24), natalizumab (n = 16), or IFN-β (n = 18) treatment. Healthy control… Show more

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Cited by 14 publications
(13 citation statements)
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“…To further validate these results, we conducted a similar experiment but exposed the cells to the cocktail of ceramide species which we identified as differentially abundant in the normal and high BMI groups of MS patients (Ceramide C16:0, C22:0, and C24:1). Each cocktail was prepared based on the physiological ceramide concentrations detected in human plasma [37,71,72] and reflected the relative high or low abundance of ceramide species detected in our lipidomic analysis. Monocytes exposed for 24 h to the cocktail corresponding to the ceramide species levels detected in the plasma samples from MS patients with high BMI showed increased proliferation and DNA methylation compared to cells exposed to the lower concentrations of ceramides, equivalent to those detected in the normal BMI MS group (Fig.…”
Section: Resultsmentioning
confidence: 99%
“…To further validate these results, we conducted a similar experiment but exposed the cells to the cocktail of ceramide species which we identified as differentially abundant in the normal and high BMI groups of MS patients (Ceramide C16:0, C22:0, and C24:1). Each cocktail was prepared based on the physiological ceramide concentrations detected in human plasma [37,71,72] and reflected the relative high or low abundance of ceramide species detected in our lipidomic analysis. Monocytes exposed for 24 h to the cocktail corresponding to the ceramide species levels detected in the plasma samples from MS patients with high BMI showed increased proliferation and DNA methylation compared to cells exposed to the lower concentrations of ceramides, equivalent to those detected in the normal BMI MS group (Fig.…”
Section: Resultsmentioning
confidence: 99%
“…That study did not consider the type of treatment. Other studies conducted on patients with II-line therapy (FG, NT) did not show an increase in OS parameters such as ceramides and the EDSS scale [ 69 ]. The short-chain ceramides stimulated oxygen species production and led to neuronal death [ 70 , 71 ].…”
Section: Discussionmentioning
confidence: 99%
“…In particular, we hypothesize that inhibition of SK activity will alter signaling through the PD-1/PD-L1 pathway such that the host immune response to the cancer is improved. This postulate is based on the observations that PD-L1 expression in tumor cells is induced by IFN-γ (Cheng et al, 2007; Dondero et al, 2016; Iwai et al, 2002; Muhlbauer et al, 2006), and IFN-γ signaling is dependent on sphingolipid metabolism (Bajwa et al, 2017; Ottenlinger et al, 2016; Seo, Alexander, & Hahm, 2011; Wakita, Nishimura, Tokura, Furukawa, & Takigawa, 1996). Furthermore, Akt- (Abdelhamed, Ogura, Yokoyama, Saiki, & Hayakawa, 2016; Atefi et al, 2014; Dong et al, 2016; Lastwika et al, 2016; Song et al, 2013; Yang et al, 2017; Zhao et al, 2017), NF-kB- (Gowrishankar et al, 2015), and TNFα- (Wang et al, 2017) signaling induce PD-L1 expression, and all of these pathways are regulated by sphingolipid signaling.…”
Section: Sphingosine Kinases As Targets For Anticancer Drugsmentioning
confidence: 99%