Interleukin-13 Propagates Prothrombin Kringle-2-Induced Neurotoxicity in Hippocampi In Vivo via Oxidative Stress.
Int J Mol Sci
; 22(7)2021 Mar 27.
Article
en En
| MEDLINE
| ID: mdl-33801783
ABSTRACT
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Protrombina
/
Estrés Oxidativo
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Interleucina-13
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Hipocampo
Límite:
Animals
Idioma:
En
Revista:
Int J Mol Sci
Año:
2021
Tipo del documento:
Article