Interleukin-1β protects astrocytes against oxidant-induced injury via an NF-κB-Dependent upregulation of glutathione synthesis

Yan He, Nicole A. Jackman, Trista L. Thorn, Valarie E. Vought, Sandra Hewett

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Astrocytes produce and export the antioxidant glutathione (GSH). Previously, we found that interleukin-1β (IL-1β) enhanced the expression of astrocyte system xc -, the transporter that delivers the rate-limiting substrate for GSH synthesis-cyst(e)ine. Herein, we demonstrate directly that IL-1β mediates a time-dependent increase in extracellular GSH levels in cortical astrocyte cultures, suggesting both enhanced synthesis and export. This increased GSH production was blocked by inhibition of nuclear factor-κB (NF-κB) activity but not by inhibition of p38 MAPK. To determine whether this increase could provide protection against oxidative stress, the oxidants tert-butyl hydroperoxide (tBOOH) and ferrous sulfate (FeSO4) were employed. IL-1β treatment prevented the increase in reactive oxygen species produced in astrocytes following tBOOH exposure. Additionally, the toxicity induced by tBOOH or FeSO4 exposure was significantly attenuated following treatment with IL-1β, an effect reversed by concomitant exposure to l-buthionine-S,R-sulfoximine (BSO), which prevented the IL-1β-mediated rise in GSH production. IL-1β failed to increase GSH or to provide protection against t-BOOH toxicity in astrocyte cultures derived from IL-1R1 null mutant mice. Overall, our data indicate that under certain conditions IL-1β may be an important stimulus for increasing astrocyte GSH production, and potentially, total antioxidant capacity in brain, via an NF-κB-dependent process.

Original languageEnglish (US)
Pages (from-to)1568-1580
Number of pages13
JournalGLIA
Volume63
Issue number9
DOIs
StatePublished - 2015

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Keywords

  • Central nervous system
  • Glioprotection
  • IL-1
  • Neuroprotection
  • Oxidative stress

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Neurology

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