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  • 标题:Cytokine-induced release of ceramide-enriched exosomes as a mediator of cell death signaling in an oligodendroglioma cell line
  • 本地全文:下载
  • 作者:Maria Podbielska ; Zdzisław M. Szulc ; Ewa Kurowska
  • 期刊名称:JLR Papers In Press
  • 印刷版ISSN:0022-2275
  • 电子版ISSN:1539-7262
  • 出版年度:2016
  • 卷号:57
  • 期号:11
  • 页码:2028-2039
  • DOI:10.1194/jlr.M070664
  • 语种:English
  • 出版社:American Society for Biochemistry and Molecular Biology
  • 摘要:Th1 pro-inflammatory cytokines, i.e., TNF-α and IFN-γ, in combination are known to induce cell death in several cell types, including oligodendrocytes, but the mechanism of their synergistic cytotoxicity is unclear. Although ceramide (Cer) has been implicated in cytokine- and stress-induced cell death, its intracellular levels alone cannot explain cytokine synergy. We considered the possibility that Cer released as part of extracellular vesicles may contribute to cytokine-induced synergistic cell death. Using a human oligodendroglioma (HOG) cell line as a model, here we show that exosomes derived from TNF-α-treated “donor” cells, while being mildly toxic to fresh cultures (similar to individual cytokines), induce enhanced cell death when added to IFN-γ-primed target cultures in a fashion resembling the effect of cytokine combination. Further, the sphingolipid profiles of secreted exosomes, as determined by HPLC-MS/MS, revealed that the treatment with the cytokines time-dependently induced the formation and exosomal release, in particular of C16-, C24-, and C24:1-Cer species; C16-, C24-, and C24:1-dihydroCer species; and C16-, C24-, and C24:1-SM species. Finally, exogenous C6-Cer or C16-Cer mimicked and enhanced the cytotoxic effects of the cytokines upon HOG cells, thereby supporting the cell death-signaling role of extracellular Cer.
  • 关键词:cell signaling ; vesicles ; lipidomics ; multiple sclerosis ; oligodendrocyte ; sphingolipids
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