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Original Article

Exp Neurobiol 2022; 31(1): 42-53

Published online February 28, 2022

© The Korean Society for Brain and Neural Sciences

Interleukin 13 on Microglia is Neurotoxic in Lipopolysaccharide-injected Striatum in vivo

Ah Reum Hong1†, Jae Geun Jang1†, Young Cheul Chung2†, So-Yoon Won3* and Byung Kwan Jin1,3*

1Department of Neuroscience, Graduate School, School of Medicine, Kyung Hee University, Seoul 02447, 2Department of Predictive Toxicology, Korea Institute of Toxicology, Daejeon 34114, 3Department of Biochemistry & Molecular Biology, School of Medicine, Kyung Hee University, Seoul 02447, Korea

Correspondence to: *To whom correspondence should be addressed.
So-Yoon Won, TEL: 82-2-961-9288, FAX: 82-2-969-4570,
Byung Kwan Jin, TEL: 82-2-961-9288, FAX: 82-2-969-4570,
These authors contributed equally to this article.

Received: October 1, 2021; Revised: February 9, 2022; Accepted: February 16, 2022

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

To explore the potential function of interleukin-13 (IL-13), lipopolysaccharide (LPS) or PBS as a control was unilaterally microinjected into striatum of rat brain. Seven days after LPS injection, there was a significant loss of neurons and microglial activation in the striatum, visualized by immunohistochemical staining against neuronal nuclei (NeuN) and the OX-42 (complement receptor type 3, CR3), respectively. In parallel, IL-13 immunoreactivity was increased as early as 3 days and sustained up to 7 days post LPS injection, compared to PBS-injected control and detected exclusively within microglia. Moreover, GFAP immunostaining and blood brain barrier (BBB) permeability evaluation showed the loss of astrocytes and disruption of BBB, respectively. By contrast, treatment with IL-13 neutralizing antibody (IL-13NA) protects NeuN+ neurons against LPS-induced neurotoxicity in vivo . Accompanying neuroprotection, IL-13NA reduced loss of GFAP+ astrocytes and damage of BBB in LPS-injected striatum. Intriguingly, treatment with IL-13NA produced neurotrophic factors (NTFs) on survived astrocytes in LPS-injected rat striatum. Taken together, the present study suggests that LPS induces expression of IL-13 on microglia, which contributes to neurodegeneration via damage on astrocytes and BBB disruption in the striatum in vivo .

Graphical Abstract

Keywords: Interleukin 13, Microglia, Neurodegeneration, Astrocytes, Neurotrophic factor, Striatum