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Article

Interleukin-13 Propagates Prothrombin Kringle-2-Induced Neurotoxicity in Hippocampi In Vivo via Oxidative Stress

by 1,†, 2,†, 3,* and 1,2,*
1
Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul 02447, Korea
2
Department of Neuroscience, Graduate School, Kyung Hee University, Seoul 02447, Korea
3
Department of Predictive Toxicology, Korea Institute of Toxicology, Daejeon 34114, Korea
*
Authors to whom correspondence should be addressed.
These authors are equally contributed.
Academic Editor: Fabrizio Michetti
Int. J. Mol. Sci. 2021, 22(7), 3486; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22073486
Received: 9 March 2021 / Revised: 24 March 2021 / Accepted: 25 March 2021 / Published: 27 March 2021
(This article belongs to the Collection Neuroinflammatory Processes in Neurodegenerative Diseases)
The present study investigated expression of endogenous interleukin-13 (IL-13) and its possible function in the hippocampus of prothrombin kringle-2 (pKr-2)-lesioned rats. Here we report that intrahippocampal injection of pKr-2 revealed a significant loss of NeuN-immunopositive (NeuN+) and Nissl+ cells in the hippocampus at 7 days after pKr-2. In parallel, pKr-2 increased IL-13 levels, which reached a peak at 3 days post pKr-2 and sustained up to 7 days post pKr-2. IL-13 immunoreactivity was seen exclusively in activated microglia/macrophages and neutrophils, but not in neurons or astrocytes. In experiments designed to explore the involvement of IL-13 in neurodegeneration, IL-13 neutralizing antibody (IL-13Nab) significantly increased survival of NeuN+ and Nissl+ cells. Accompanying neuroprotection, immunohistochemical analysis indicated that IL-13Nab inhibited pKr-2-induced expression of inducible nitric oxide synthase and myeloperoxidase within activated microglia/macrophages and neutrophils, possibly resulting in attenuation of reactive oxygen species (ROS) generation and oxidative damage of DNA and protein. The current findings suggest that the endogenous IL-13 expressed in pKr-2 activated microglia/macrophages and neutrophils might be harmful to hippocampal neurons via oxidative stress. View Full-Text
Keywords: interleukin-13 (IL-13); prothrombin kringle-2 (pKr-2); microglia/macrophages and neutrophils; oxidative/nitrosative stress; reactive oxygen species (ROS) interleukin-13 (IL-13); prothrombin kringle-2 (pKr-2); microglia/macrophages and neutrophils; oxidative/nitrosative stress; reactive oxygen species (ROS)
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MDPI and ACS Style

Jeong, J.Y.; Wi, R.; Chung, Y.C.; Jin, B.K. Interleukin-13 Propagates Prothrombin Kringle-2-Induced Neurotoxicity in Hippocampi In Vivo via Oxidative Stress. Int. J. Mol. Sci. 2021, 22, 3486. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22073486

AMA Style

Jeong JY, Wi R, Chung YC, Jin BK. Interleukin-13 Propagates Prothrombin Kringle-2-Induced Neurotoxicity in Hippocampi In Vivo via Oxidative Stress. International Journal of Molecular Sciences. 2021; 22(7):3486. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22073486

Chicago/Turabian Style

Jeong, Jae Y.; Wi, Rayul; Chung, Young C.; Jin, Byung K. 2021. "Interleukin-13 Propagates Prothrombin Kringle-2-Induced Neurotoxicity in Hippocampi In Vivo via Oxidative Stress" Int. J. Mol. Sci. 22, no. 7: 3486. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22073486

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