دورية أكاديمية

Activation of the NLRP3 inflammasome in microglia: the role of ceramide.

التفاصيل البيبلوغرافية
العنوان: Activation of the NLRP3 inflammasome in microglia: the role of ceramide.
المؤلفون: Scheiblich, Hannah, Schlütter, Anna, Golenbock, Douglas T, Latz, Eicke, Martinez-Martinez, Pilar, Heneka, Michael T
المصدر: Journal of neurochemistry 143(5), 534-550 (2017). doi:10.1111/jnc.14225
بيانات النشر: Wiley-Blackwell
سنة النشر: 2017
مصطلحات موضوعية: info:eu-repo/classification/ddc/610, Animals, Carrier Proteins: metabolism, Cells, Cultured, Ceramides: pharmacology, Cytoskeletal Proteins: metabolism, Inflammasomes: drug effects, Inflammasomes: metabolism, Interleukin-1beta: metabolism, Macrophages: metabolism, Mice, Microglia: drug effects, Microglia: metabolism, NLR Family, Pyrin Domain-Containing 3 Protein: metabolism, Reactive Oxygen Species: metabolism, Carrier Proteins, Ceramides, Cytoskeletal Proteins, Inflammasomes, Interleukin-1beta, Pyrin Domain-Containing 3 Protein, Nlrp3 protein, mouse, Reactive Oxygen Species
جغرافية الموضوع: DE
الوصف: Inflammation within the CNS is a major component of many neurodegenerative diseases. A characteristic feature is the generation of microglia-derived factors that play an essential role in the immune response. IL-1β is a pro-inflammatory cytokine released by activated microglia, able to exacerbate injury at elevated levels. In the presence of caspase-1, pro-IL-1β is cleaved to the mature cytokine following NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome activation. Growing evidence suggests that ceramide plays a critical role in NLRP3 inflammasome assembly, however, the relationship between ceramide and inflammasome activation in microglia remains unknown. Here, we investigated potential mechanistic links between ceramide as a modulator of NLRP3 inflammasome assembly and the resulting secretion of IL-1β using small bioactive enzyme stimulators and inhibitors of ceramide signaling in wild-type and apoptosis-associated speck-like protein containing a CARD knockout (ASC-/- ) primary microglia. To induce the expression of inflammasome components, microglia were primed prior to experiments. Treatment with sodium palmitate (PA) induced de novo ceramide synthesis via modulation of its synthesizing protein serine palmitoyl transferase resulting in increased IL-1β secretion in microglia. Exposure of microglia to the serine palmitoyl transferase-inhibitor l-cycloserine significantly prevented PA-induced IL-1β secretion. Application of the ceramide analogue C2 and the sphingosine-1-phosphate-receptor agonist Fingolimod (FTY720) up-regulated levels of IL-1β and cleaved caspase-1 in wild-type microglia, whereas ASC-/- microglia were unaffected. HPA-12 inhibition of ceramide transport did not affect inflammasome activation. Taken together, our findings reveal a critical role for ceramide as a positive modulator of NLRP3 inflammasome assembly and the resulting release of IL-1β.
نوع الوثيقة: article in journal/newspaper
اللغة: English
العلاقة: info:eu-repo/semantics/altIdentifier/pmid/pmid:28940479; info:eu-repo/semantics/altIdentifier/issn/0022-3042; info:eu-repo/semantics/altIdentifier/issn/1471-4159; https://pub.dzne.de/record/139624Test; https://pub.dzne.de/search?p=id:%22DZNE-2020-05946%22Test
الإتاحة: https://doi.org/10.1111/jnc.14225Test
https://pub.dzne.de/record/139624Test
https://pub.dzne.de/search?p=id:%22DZNE-2020-05946%22Test
حقوق: info:eu-repo/semantics/closedAccess
رقم الانضمام: edsbas.1BEE601
قاعدة البيانات: BASE