Cited by 84Neuroinflammation and Neurodegeneration MechanismsNeurological Disease Mechanisms and TreatmentsTryptophan and brain disorders

IL-13-induced oxidative stress via microglial NADPH oxidase contributes to death of hippocampal neurons in vivo

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Park, Keun W, Baik, Hyung H, Jin, Byung K·2009·The Journal of Immunology

Abstract

In the present study, we investigated the effects of IL-13, a well-known anti-inflammatory cytokine, on the thrombin-treated hippocampus in vivo. NeuN immunohistochemistry and Nissl staining revealed significant loss of hippocampal CA1 neurons upon intrahippocampal injection of thrombin. This neurotoxicity was accompanied by substantial microglial activation, as evident from OX-42 immunohistochemistry results. In parallel, Western blot analysis and hydroethidine histochemistry disclosed activation of NADPH oxidase, generation of reactive oxygen species, and oxidative damage in the hippocampal CA1 area showing hippocampal neuron degeneration. Interestingly, immunohistochemical and biochemical experiments showed that intrahippocampal injection of thrombin increased IL-13 immunoreactivity and IL-13 levels as early as 8 h after thrombin, reaching a peak at 7 days, which was maintained up to 14 days. Moreover, double-label immunohistochemistry revealed IL-13 immunoreactivity exclusively in activated microglia. IL-13-neutralizing Abs significantly rescued CA1 hippocampal neurons from thrombin neurotoxicity. In parallel, neutralization of IL-13 inhibited activation of NADPH oxidase, reactive oxygen species production, and oxidative damage. Additionally, IL-13 neutralization suppressed the expression of inducible NO synthase and several proinflammatory cytokines. To our knowledge, the present study is the first to show that IL-13 triggers microglial NADPH oxidase-derived oxidative stress, leading to the degeneration of hippocampal neurons in vivo, as occurs in cases of Alzheimer's disease.

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Authors
Park, K. W., Baik, H. H., & Jin, B. K.
Affiliations
  • Department of Biochemistry & Molecular biology
  • Kyung Hee University (KR)
Venue
The Journal of Immunology
Published
2009-10-01
Volume
183
Issue
7
Pages
4666-4674
ISSN
  • 0022-1767 (ISSN-L)
  • 1550-6606
OpenAlex
W2159118237
Cited by
84
References
57
Citations by year
2025: 4 · 2024: 4 · 2023: 2 · 2022: 6 · 2021: 8 · 2020: 8 · 2019: 7 · 2018: 5 · 2017: 5 · 2016: 1 · 2015: 6 · 2014: 9 · 2013: 2 · 2012: 8
FWCI
3.40
Type
journal article
Language
en
Open access
Locations
  • The Journal of Immunology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Kyung Hee University
  • Korea Science and Engineering Foundation
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
Keywords
IL-13, NADPH oxidase, oxidative stress, microglial activation, CA1 pyramidal neurons, reactive oxygen species, neurodegeneration, inducible nitric oxide synthase, inflammatory cytokines, Alzheimer's disease, neuroinflammation
MeSH terms
Animals, Enzyme Activation, Female, Hippocampus, Neurons, Thrombin, Up-Regulation, Gene Expression Regulation, Enzymologic, Rats, Sprague-Dawley, Apoptosis, Microglia, Oxidative Stress, Interleukin-13, NADPH Oxidases, Rats

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