Interleukin-1? Protects Neurons against Oxidant-Induced Injury via the Promotion of Astrocyte Glutathione Production.

ABSTRACT: Interleukin-1? (IL-1?), a key cytokine that drives neuroinflammation in the Central Nervous System (CNS), is enhanced in many neurological diseases/disorders. Although IL-1? contributes to and/or sustains pathophysiological processes in the CNS, we recently demonstrated that IL-1? can protect cortical astrocytes from oxidant injury in a glutathione (GSH)-dependent manner. To test whether IL-1? 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-1? 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-1? in association with enhanced GSH production/release. IL-1? 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-1?. 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-1? 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.

SUBMITTER: Chowdhury T 

PROVIDER: S-EPMC6115796 | biostudies-literature |

REPOSITORIES: biostudies-literature