Title

Interleukin-13/-4-Induced Oxidative Stress Contributes To Death Of Hippocampal Neurons In Aβ 1-42-Treated Hippocampus In Vivo

Abstract

Aims: The present study examined whether Aβ 1-42 can induce endogenous expression of interleukin-13 (IL-13) or (IL-4) within activated microglia in the rat hippocampus in vivo. We further investigated whether these cytokines mediate ROS/RNS generation through activation of NADPH oxidase and/or inducible nitric oxide synthase (iNOS), and thus contribute to the degeneration of hippocampal neurons in vivo. Results: Here, we show that IL-13 and IL-4, endogenously expressed in Aβ 1-42-activated microglia in hippocampus in vivo, contribute to degeneration of hippocampal neurons in vivo. Neutralization of IL-13 and IL-4 protected hippocampal neurons in vivo against neurotoxicity by inhibiting activation of microglial NADPH oxidase and iNOS, resulting in attenuation of ROS generation and oxidative damage of protein, lipid and DNA. Innovation: To our knowledge, this is the first study to demonstrate the possible involvement of endogenously expressed IL-13 and/or IL-4 in activated microglia after Aβ 1-42 injection in the degeneration of hippocampal neurons in vivo. The current findings suggest that the deleterious effects of microglia-derived endogenous IL-13 and/or IL-4 are involved in oxidative stress-mediated neurodegenerative diseases, such as AD. Conclusion: We carefully hypothesize that IL-13 and IL-4, well-known as anti-inflammatory cytokines might serve as neurotoxic mediators by enhancing microglia-derived oxidative stress in Aβ 1-42-treated hippocampus in vivo. © 2012, Mary Ann Liebert, Inc.

Publication Date

6-15-2012

Publication Title

Antioxidants and Redox Signaling

Volume

16

Issue

12

Number of Pages

1369-1383

Document Type

Article

Personal Identifier

scopus

DOI Link

https://doi.org/10.1089/ars.2011.4175

Socpus ID

84860120752 (Scopus)

Source API URL

https://api.elsevier.com/content/abstract/scopus_id/84860120752

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