Interleukin-1β Protects Neurons against Oxidant-Induced Injury via the Promotion of Astrocyte Glutathione Production
AbstractInterleukin-1β (IL-1β), a key cytokine that drives neuroinflammation in the Central Nervous System (CNS), is enhanced in many neurological diseases/disorders. Although IL-1β contributes to and/or sustains pathophysiological processes in the CNS, we recently demonstrated that IL-1β can protect cortical astrocytes from oxidant injury in a glutathione (GSH)-dependent manner. To test whether IL-1β could similarly protect neurons against oxidant stress, near pure neuronal cultures or mixed cortical cell cultures containing neurons and astrocytes were exposed to the organic peroxide, tert-butyl hydroperoxide (t-BOOH), following treatment with IL-1β or its vehicle. Neurons and astrocytes in mixed cultures, but not pure neurons, were significantly protected from the toxicity of t-BOOH following treatment with IL-1β in association with enhanced GSH production/release. IL-1β failed to increase the GSH levels or to provide protection against t-BOOH toxicity in chimeric mixed cultures consisting of IL-1R1+/+ neurons plated on top of IL-1R1−/− astrocytes. The attenuation of GSH release via block of multidrug resistance-associated protein 1 (MRP1) transport also abrogated the protective effect of IL-1β. These protective effects were not strictly an in vitro phenomenon as we found an increased striatal vulnerability to 3-nitropropionic acid-mediated oxidative stress in IL-1R1 null mice. Overall, our data indicate that IL-1β protects neurons against oxidant injury and that this likely occurs in a non-cell-autonomous manner that relies on an increase in astrocyte GSH production and release. View Full-Text
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Chowdhury, T.; Allen, M.F.; Thorn, T.L.; He, Y.; Hewett, S.J. Interleukin-1β Protects Neurons against Oxidant-Induced Injury via the Promotion of Astrocyte Glutathione Production. Antioxidants 2018, 7, 100.
Chowdhury T, Allen MF, Thorn TL, He Y, Hewett SJ. Interleukin-1β Protects Neurons against Oxidant-Induced Injury via the Promotion of Astrocyte Glutathione Production. Antioxidants. 2018; 7(8):100.Chicago/Turabian Style
Chowdhury, Twinkle; Allen, Matthew F.; Thorn, Trista L.; He, Yan; Hewett, Sandra J. 2018. "Interleukin-1β Protects Neurons against Oxidant-Induced Injury via the Promotion of Astrocyte Glutathione Production." Antioxidants 7, no. 8: 100.
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