title: Interleukin 15 activates Akt to protect astrocytes from oxygen glucose deprivation-induced cell death.
abstract: Astrocytes play a pivotal role in neuronal survival under the condition of post-ischemic brain inflammation, but the relevant astrocyte-derived mediators of ischemic brain injury remain to be defined. IL-15 supports survival of multiple lymphocyte lineages in the peripheral immune system, but the role of IL-15 in inflammatory disease of the central nervous system is not well defined. Recent research has shown an increase of IL-15-expressing astrocytes in the ischemic brain. Since astrocytes promote neuron survival under cerebral ischemia by buffering excess extracellular glutamate and producing growth factors, recovery of astrocyte function could be of benefit for stroke therapy. Here, we report that IL-15 is the pro-survival cytokine that prevents astrocyte death from oxygen glucose deprivation (OGD)-induced damage. Astrocytes up-regulate expression of the IL-15/IL-15Rα complex under OGD, whereas OGD down-regulates the levels of pSTAT5 and pAkt in astrocytes. IL-15 treatment ameliorates the decline of pAkt, decreases the percentage of annexin V+cells, inhibits the activation of caspase-3, and activates the Akt pathway to promote astrocyte survival in response to OGD. We further identified that activation of Akt, but not PKCα/βI, is essential for astrocyte survival under OGD. Taken together, this study reveals the function of IL-15 in astrocyte survival via Akt phosphorylation in response to OGD-induced damage.
authors.affiliation: Department of Medical Research, Taipei Medical University Hospital, Taipei, Taiwan; Department of Health Healing and Health Marketing, Kainan University, Taoyuan, Taiwan.
authors.forename: Gilbert Aaron
authors.initials: GA
authors.lastname: Lee
authors.affiliation: Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan.
authors.forename: Yein-Gei
authors.initials: YG
authors.lastname: Lai
authors.affiliation: Department of Medical Research, Taipei Medical University Hospital, Taipei, Taiwan.
authors.forename: Ray-Jade
authors.initials: RJ
authors.lastname: Chen
authors.affiliation: Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan.
authors.forename: Nan-Shih
authors.initials: NS
authors.lastname: Liao
mesh_terms: D000818:Animals; D017304:Annexin A5 / Q000276:immunology; D001253:Astrocytes / Q000276:immunology*; D016923:Cell Death / Q000276:immunology; D015687:Cell Hypoxia / Q000276:immunology; D004789:Enzyme Activation / Q000187:drug effects / Q000276:immunology; D005947:Glucose / Q000276:immunology; D019409:Interleukin-15 / Q000276:immunology / Q000494:pharmacology*; D051379:Mice; D010100:Oxygen / Q000276:immunology; D051057:Proto-Oncogene Proteins c-akt / Q000276:immunology*; D053647:Receptors, Interleukin-15 / Q000276:immunology; D050799:STAT5 Transcription Factor / Q000276:immunology
chemical_list: D017304:Annexin A5; C508025:Il15ra protein, mouse; D019409:Interleukin-15; D053647:Receptors, Interleukin-15; D050799:STAT5 Transcription Factor; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose; D010100:Oxygen
keywords: Akt; Astrocyte; IL-15; Oxygen glucose deprivation; PKC