Oxysterol levels and metabolism in the course of neuroinflammation: insights from in vitro and in vivo models

Mutemberezi, Valentin; Buisseret, Baptiste; Masquelier, Julien; Guillemot-Legris, Owein; Alhouayek, Mireille; Muccioli, Giulio G.

doi:10.1186/s12974-018-1114-8

Cited by 50 publications

(53 citation statements)

References 74 publications

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“…This is in line with another study, in which microglia up‐regulated their expression of CH25H during remyelination after toxin‐induced demyelination in the cuprizone mouse model . A recent study supported these findings, by showing that LPS treatment of a microglia cell line led to increased CH25H expression . However, the study also found that the production of the EBI2 ligands 7α,25‐OHC and 7α,27‐OHC was decreased, rather than increased, in response to LPS treatment, presumably due to an increased expression of HSD3B7 and a decreased expression of CYP27A1.…”

Section: Ebi2 In Local Immunity and Autoimmune Diseasessupporting

confidence: 88%

“…However, EBI2 signaling induced by 7α,25‐OHC in astrocytes was shown to decrease their production of pro‐inflammatory cytokines, including IL‐6 and TNF‐α, in response to LPS or IL‐17/TNF‐α treatment . Interestingly, a similar effect was seen using the microglia and astrocyte co‐culture described above, where treatment of LPS‐activated cells with 7α,25‐OHC, and other EBI2 ligands, significantly decreased the production of the pro‐inflammatory cytokine IL‐1β . A similar effect was demonstrated in vivo.…”

Section: Ebi2 In Local Immunity and Autoimmune Diseasesmentioning

confidence: 52%

“…A similar effect was demonstrated in vivo. In WT mice, intraperitoneal LPS injections, resulting in brain inflammation characterized by increased IL‐6 and TNF‐α expression, also resulted in increased levels of 7α,25‐OHC in the brain . In EBI2‐deficient mice, treatment with LPS resulted in significantly increased levels of IL‐6 and TNF‐α in their brains compared to WT mice .…”

Section: Ebi2 In Local Immunity and Autoimmune Diseasesmentioning

confidence: 99%

“…However, the study also found that the production of the EBI2 ligands 7α,25‐OHC and 7α,27‐OHC was decreased, rather than increased, in response to LPS treatment, presumably due to an increased expression of HSD3B7 and a decreased expression of CYP27A1. But intriguingly, when primary microglia were co‐cultured with primary astrocytes, thus more accurately mimicking the situation in vivo, the levels of 7α,25‐OHC and 7α,27‐OHC were increased in the co‐culture by LPS treatment …”

Section: Ebi2 In Local Immunity and Autoimmune Diseasesmentioning

confidence: 99%

“…Among these so‐called encephalitogenic T cells, Th17 cells expressing IL‐17 have been shown to play a crucial role for the pathogenesis of the disease . Interestingly, changes in oxysterol levels have been detected in the CNS of EAE animals as well as in MS patients (Fig. ).…”

Section: Ebi2 In Local Immunity and Autoimmune Diseasesmentioning

confidence: 99%

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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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Section: Ebi2 In Local Immunity and Autoimmune Diseasessupporting

confidence: 88%

Section: Ebi2 In Local Immunity and Autoimmune Diseasesmentioning

confidence: 52%

Section: Ebi2 In Local Immunity and Autoimmune Diseasesmentioning

confidence: 99%

Section: Ebi2 In Local Immunity and Autoimmune Diseasesmentioning

confidence: 99%

Section: Ebi2 In Local Immunity and Autoimmune Diseasesmentioning

confidence: 99%

See 3 more Smart Citations

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 Role of Cholesterol in α‐Synuclein and Lewy Body Pathology in GBA1 Parkinson's Disease

2020

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A BS TRACT: Parkinson's disease (PD) is a progressive neurodegenerative disease where dopaminergic neurons in the substantia nigra are lost, resulting in a decrease in striatal dopamine and, consequently, motor control. Dopaminergic degeneration is associated with the appearance of Lewy bodies, which contain membrane structures and proteins, including α-synuclein (α-Syn), in surviving neurons. PD displays a multifactorial pathology and develops from interactions between multiple elements, such as age, environmental conditions, and genetics. Mutations in the GBA1 gene represent one of the major genetic risk factors for PD. This gene encodes an essential lysosomal enzyme called β-glucocerebrosidase (GCase), which is responsible for degrading the glycolipid glucocerebroside into glucose and ceramide. GCase can generate glucosylated cholesterol via transglucosylation and can also degrade the sterol glucoside. Although the molecular mechanisms that predispose an individual to neurodegeneration remain unknown, the role of cholesterol in PD pathology deserves consideration. Disturbed cellular cholesterol metabolism, as reflected by accumulation of lysosomal cholesterol in GBA1-associated PD cellular models, could contribute to changes in lipid rafts, which are necessary for synaptic localization and vesicle cycling and modulation of synaptic integrity. α-Syn has been implicated in the regulation of neuronal cholesterol, and cholesterol facilitates interactions between α-Syn oligomers. In this review, we integrate the results of previous studies and describe the cholesterol landscape in cellular homeostasis and neuronal function. We discuss its implication in α-Syn and Lewy body pathophysiological mechanisms underlying PD, focusing on the role of GCase and cholesterol.

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Histone Deacetylase 2 Inhibitor CAY10683 Alleviates Lipopolysaccharide Induced Neuroinflammation Through Attenuating TLR4/NF-κB Signaling Pathway

et al. 2018

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Neuroinflammation involves in the progression of many central nervous system diseases. Several studies have shown that histone deacetylase (HDAC) inhibitors modulated inflammatory responses in lipopolysaccharide (LPS) stimulated microglia. While, the mechanism is still unclear. The aim of present study was to investigate the effect of HDAC2 inhibitor CAY10683 on inflammatory responses and TLR4/NF-κB signaling pathways in LPS activated BV2 microglial cells and LPS induced mice neuroinflammation. The effect of CAY10683 on cell viability of BV2 microglial cells was detected by CCK-8 assay. The expressions of inflammatory cytokines were analyzed by western blotting and RT-PCR respectively. The TLR4 protein expression was measured by western blotting, immunofluorescence, immunohistochemistry respectively. The protein expressions of MYD88, phospho-NF-κB p65, NF-κB-p65, acetyl-H3 (AH3), H3, and HDAC2 were analyzed by western blotting. We found that CAY10683 could inhibit expression levels of inflammatory cytokine TNF-α and IL-1β in LPS activated BV2 microglial cells and LPS induced mice neuroinflammation. It could induce TLR4, MYD88, phospho-NF-κB p65, and HDAC2 expressions. Moreover, CAY10683 increased the acetylation of histones H3 in LPS activated BV2 microglial cells and LPS induced mice neuroinflammation. Taken together, our findings suggested that HDAC2 inhibitor CAY10683 could suppress neuroinflammatory responses and TLR4/NF-κB signaling pathways by acetylation after LPS stimulation.

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Oxysterol levels and metabolism in the course of neuroinflammation: insights from in vitro and in vivo models

Cited by 50 publications

References 74 publications

EBI2 in splenic and local immune responses and in autoimmunity

EBI2 in splenic and local immune responses and in autoimmunity

The Role of Cholesterol in α‐Synuclein and Lewy Body Pathology in GBA1 Parkinson's Disease

Histone Deacetylase 2 Inhibitor CAY10683 Alleviates Lipopolysaccharide Induced Neuroinflammation Through Attenuating TLR4/NF-κB Signaling Pathway

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