EBI2 regulates intracellular signaling and migration in human astrocyte

Rutkowska, Aleksandra; Preuß, Inga; Gessier, François; Sailer, Andreas W.; Dev, Kumlesh K.

doi:10.1002/glia.22757

Cited by 60 publications

(71 citation statements)

References 36 publications

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“…Human, rat and mouse astrocytes were cultured as we have described before (Healy et al, 2013;Rutkowska et al, 2015). BV2 microglia were cultured in DMEM supplemented with 2% FBS (Labtech) and 1% penicillin/ streptomycin (Sigma) at 37°C and 5% CO 2 .…”

Section: Astrocyte and Cerebellar Slice Culturesmentioning

confidence: 99%

“…This wash step was repeated and the emission spectra at 535 nm and 590 nm was measured (SpectraMAX Gemini XS). A colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to assess cell viability as per manufacturer's instructions (Invitrogen, M6494), similar to our previous studies (Mullershausen et al, 2009;Rutkowska et al, 2015).…”

Section: Jc-1 and Mtt Assaysmentioning

confidence: 99%

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Galactosylsphingosine (psychosine)-induced demyelination is attenuated by sphingosine 1-phosphate signalling

O’Sullivan

Dev

2015

Journal of Cell Science

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Globoid cell leukodystrophy (Krabbe disease) is a rare infantile neurodegenerative disorder. Krabbe disease is caused by deficiency in the lysosomal enzyme galactocerebrosidase (GALC) resulting in accumulation, in the micromolar range, of the toxic metabolite galactosylsphingosine ( psychosine) in the brain. Here we find that psychosine induces human astrocyte cell death probably via an apoptotic process in a concentration-and time-dependent manner (EC50∼15 μM at 4 h). We show these effects of psychosine are attenuated by pre-treatment with the sphingosine 1-phosphate receptor agonist pFTY720 (fingolimod) (IC50∼100 nM). Psychosine (1 μM, 10 μM) also enhances LPS-induced (EC50∼100 ng/ml) production of pro-inflammatory cytokines in mouse astrocytes, which is also attenuated by pFTY720 (1 μM). Most notably, for the first time, we show that psychosine, at a concentration found in the brains of patients with Krabbe disease (EC50∼100 nM), directly induces demyelination in mouse organotypic cerebellar slices in a manner that is independent of pro-inflammatory cytokine response and that pFTY720 (0.1 nM) significantly inhibits. These results support the idea that psychosine is a pathogenic agent in Krabbe disease and suggest that sphingosine 1-phosphate signalling could be a potential drug target for this disorder.

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Section: Astrocyte and Cerebellar Slice Culturesmentioning

confidence: 99%

Section: Jc-1 and Mtt Assaysmentioning

confidence: 99%

Galactosylsphingosine (psychosine)-induced demyelination is attenuated by sphingosine 1-phosphate signalling

O’Sullivan

Dev

2015

Journal of Cell Science

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“…Astrocyte expressing HSD3B7 is responsible for degradation of oxysterol, the active oxidized product of cholesterol, which can be used as a marker of brain atrophy in patients holding aging neurons with AD and HD (Leoni & Caccia, 2011; Rutkowska, Preuss, Gessier, Sailer, & Dev, 2015). Additionally, the production of the dafachronic acids, a nuclear receptor for bile acids, can be regulated by a conserved 3 beta‐ HSD to participate in cholesterol, bile acid metabolism, and longevity (Wollam et al., 2012).…”

Section: Discussionmentioning

confidence: 99%

The association between HSD3B7 gene variant and Parkinson's disease in ethnic Chinese

Wang

Sun

et al. 2018

Brain and Behavior

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ObjectivesStudies at the genomewide level of Parkinson's disease (PD) suggested a significant association between the Hydroxy‐delta‐5‐steroid dehydrogenase, 3 beta‐ and steroid delta isomerase 7 (HSD3B7) gene rs9938550 variant and a decreased risk for PD. But its effect has only been discussed in Caucasian populations, and no phenotypic characteristics were included. To investigate the novel variant for PD in Chinese Han populations, we performed an association analysis of rs9938550 variant in a large cohort.MethodsUsing a case–control methodology, a total of 2,239 subjects (1,072 sporadic patients with PD and 1,167 control) were genotyped and the genetic association was analyzed.ResultsNo significant association was found between allele A of rs9938550 and PD in the entire cohort (p = .079). However, the frequency of allele A was lower in late‐onset PD (LOPD) as compared with controls older than 50 years (OR = 0.62, 95% CI: 0.45–0.85, p adjust = .002). Relatively lower Unified Parkinson's Disease Rating Scale scores were demonstrated in mid‐ to late‐stage PD with GA + AA genotypes than GG genotype (p adjust = .018), while other clinical features were similar between carriers and noncarriers.ConclusionsOur results support that the HSD3B7 rs9938550 variant, which is likely linked to bile acid biosynthesis, reduces the risk of LOPD in Chinese patients and might induce a benign clinical performance.

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“…). Furthermore, analysis of EBI2 signaling revealed increased phosphorylation of ERK as well as Ca 2+ mobilization upon stimulation with 7α,25‐OHC in a dose‐dependent manner . Although murine astrocytes were found to migrate toward 7α,25‐OHC in an EBI2‐dependent manner, no major differences in localization or numbers of astrocytes were observed in vivo in the absence of EBI2 .…”

Section: Ebi2 In Local Immunity and Autoimmune Diseasesmentioning

confidence: 96%

“…The astrocyte is the only glial cell type in which the expression and function of EBI2 has been characterized. Rutkowska and colleagues found expression of EBI2 in human and murine astrocytes, and murine astrocytes were found to express all enzymes necessary for the synthesis and degradation of 7α,25‐OHC (Fig. ).…”

Section: Ebi2 In Local Immunity and Autoimmune Diseasesmentioning

confidence: 98%

EBI2 in splenic and local immune responses and in autoimmunity

Barington

Wanke

Arfelt

et al. 2018

Journal of Leukocyte Biology

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The seven transmembrane G protein-coupled receptor EBV-induced gene 2 (EBI2), also known as GPR183, is expressed in particular in immune cells. Activated by its endogenous ligands, which are a group of oxysterols, it functions as a chemo-attractant receptor, mediating cell migration. In coordination with other receptors, EBI2 plays important roles in controlling the migration of immune cells during the course of a T-dependent Ab response in the spleen. In recent years, it has become clear that EBI2 also has other roles to play in the immune system. Thus, EBI2 seems to be involved in innate immune responses, such as those mediated by TLR signaling, and it has been implicated in regional immune responses, including immune responses in the CNS. In this review, we describe the functions of EBI2 in B cells, T cells, and dendritic cells during the course of a T-dependent Ab response in the spleen. Furthermore, we review the existing evidence supporting a role for EBI2 in local immune responses and in autoimmune diseases, with a special focus on immune responses in the CNS. Finally, we discuss which type of role EBI2 may play in autoimmune diseases, and we give our opinion about the paths of future research in EBI2.

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EBI2 regulates intracellular signaling and migration in human astrocyte

Cited by 60 publications

References 36 publications

Galactosylsphingosine (psychosine)-induced demyelination is attenuated by sphingosine 1-phosphate signalling

Galactosylsphingosine (psychosine)-induced demyelination is attenuated by sphingosine 1-phosphate signalling

The association between HSD3B7 gene variant and Parkinson's disease in ethnic Chinese

EBI2 in splenic and local immune responses and in autoimmunity

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