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Interleukin‐1β protects astrocytes against oxidant‐induced injury via an NF ‐κ B ‐Dependent upregulation of glutathione synthesis
Author(s) -
He Yan,
Jackman Nicole A.,
Thorn Trista L.,
Vought Valarie E.,
Hewett Sandra J.
Publication year - 2015
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.22828
Subject(s) - glutathione , astrocyte , downregulation and upregulation , oxidative stress , buthionine sulfoximine , biology , biochemistry , neuroglia , reactive oxygen species , antioxidant , pharmacology , chemistry , microbiology and biotechnology , endocrinology , enzyme , gene , central nervous system
Astrocytes produce and export the antioxidant glutathione (GSH). Previously, we found that interleukin‐1β (IL‐1β) enhanced the expression of astrocyte system x c − , 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 (FeSO 4 ) 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 FeSO 4 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. GLIA 2015;63:1568–1580