Title

Interleukin-13/-4-Induced Oxidative Stress Contributes to Death of Hippocampal Neurons in A beta(1-42)-Treated Hippocampus In Vivo

Authors

Authors

J. H. Nam; K. W. Park; E. S. Park; Y. B. Lee; H. G. Lee; H. H. Baik; Y. S. Kim; S. Maeng; J. Park;B. K. Jin

Comments

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Abbreviated Journal Title

Antioxid. Redox Signal.

Keywords

AMYLOID PRECURSOR PROTEIN; MICROGLIAL NADPH OXIDASE; ALZHEIMERS-DISEASE; NITRIC-OXIDE; AUTOIMMUNE ENCEPHALOMYELITIS; NEUROPROTECTIVE ROLE; ACTIVATED MICROGLIA; EXPERIMENTAL-MODEL; GLIAL ACTIVATION; BETA-PROTEIN; Biochemistry & Molecular Biology; Endocrinology & Metabolism

Abstract

Aims: The present study examined whether A beta(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 A beta(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 A beta(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 A beta(1-42)-treated hippocampus in vivo. Antioxid. Redox Signal. 16, 1369-1383.

Journal Title

Antioxidants & Redox Signaling

Volume

16

Issue/Number

12

Publication Date

1-1-2012

Document Type

Article

Language

English

First Page

1369

Last Page

1383

WOS Identifier

WOS:000303047100001

ISSN

1523-0864

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