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Open Access Research

Soybean-derived Bowman-Birk inhibitor inhibits neurotoxicity of LPS-activated macrophages

Jieliang Li1, Li Ye1, Denise R Cook2, Xu Wang1, Jinping Liu1, Dennis L Kolson2, Yuri Persidsky1 and Wen-Zhe Ho13*

Author Affiliations

1 Department of Pathology & Laboratory Medicine, Temple University School of Medicine, Philadelphia, Pennsylvania, USA

2 Department of Neurology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA

3 Animal Biosafety Level 3 Laboratory, Wuhan University, Wuhan, 430071 PR China

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Journal of Neuroinflammation 2011, 8:15  doi:10.1186/1742-2094-8-15

Published: 15 February 2011

Abstract

Background

Lipopolysaccharide (LPS), the major component of the outer membrane of gram-negative bacteria, can activate immune cells including macrophages. Activation of macrophages in the central nervous system (CNS) contributes to neuronal injury. Bowman-Birk inhibitor (BBI), a soybean-derived protease inhibitor, has anti-inflammatory properties. In this study, we examined whether BBI has the ability to inhibit LPS-mediated macrophage activation, reducing the release of pro-inflammatory cytokines and subsequent neurotoxicity in primary cortical neural cultures.

Methods

Mixed cortical neural cultures from rat were used as target cells for testing neurotoxicity induced by LPS-treated macrophage supernatant. Neuronal survival was measured using a cell-based ELISA method for expression of the neuronal marker MAP-2. Intracellular reactive oxygen species (ROS) production in macrophages was measured via 2', 7'-dichlorofluorescin diacetate (DCFH2DA) oxidation. Cytokine expression was determined by quantitative real-time PCR.

Results

LPS treatment of macrophages induced expression of proinflammatory cytokines (IL-1β, IL-6 and TNF-α) and of ROS. In contrast, BBI pretreatment (1-100 μg/ml) of macrophages significantly inhibited LPS-mediated induction of these cytokines and ROS. Further, supernatant from BBI-pretreated and LPS-activated macrophage cultures was found to be less cytotoxic to neurons than that from non-BBI-pretreated and LPS-activated macrophage cultures. BBI, when directly added to the neuronal cultures (1-100 μg/ml), had no protective effect on neurons with or without LPS-activated macrophage supernatant treatment. In addition, BBI (100 μg/ml) had no effect on N-methyl-D-aspartic acid (NMDA)-mediated neurotoxicity.

Conclusions

These findings demonstrate that BBI, through its anti-inflammatory properties, protects neurons from neurotoxicity mediated by activated macrophages.