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Int. J. Mol. Sci. 2016, 17(1), 25; doi:10.3390/ijms17010025

Interleukin-10 Protection against Lipopolysaccharide-Induced Neuro-Inflammation and Neurotoxicity in Ventral Mesencephalic Cultures

1
School of Biological & Basic Medical Sciences, Soochow University, 199 Renai Road, Suzhou 215123, China
2
Department of Physiology, School of Medicine, and Co-innovation Center of Neuroregeneration, Nantong University, 19 Qixiu Road, Nantong 226001, China
*
Authors to whom correspondence should be addressed.
Academic Editor: Katalin Prokai-Tatrai
Received: 1 July 2015 / Revised: 13 November 2015 / Accepted: 18 December 2015 / Published: 28 December 2015
(This article belongs to the Special Issue Neuroprotective Strategies 2015)
View Full-Text   |   Download PDF [3199 KB, uploaded 28 December 2015]   |  

Abstract

Interleukin (IL)-10, an anti-inflammatory cytokine, is expressed in the brain and can inhibit microglial activation. Herein, we utilized lipopolysaccharide (LPS)-induced inflammatory Parkinson’s disease (PD) cell model to determine whether microglia and astrocytes are necessary targets for IL-10 neuroprotection. Primary ventral mesencephalic (VM) cultures with different composition of neurons, microglia and astrocytes were prepared. The cells were exposed to IL-10 (15, 50 or 150 ng/mL) 1 h prior to LPS (50 ng/mL) treatment. LPS induced dopaminergic and non-dopaminergic neuronal loss in VM cultures, VM neuron-enriched cultures, and neuron-microglia co-cultures, but not in neuron-astrocyte co-cultures. IL-10 reduced LPS-induced neuronal loss particularly in single VM neuron cultures. Pro-inflammatory mediators (TNF-α, IL-1β, inducible nitric oxide synthase and cyclooxygenase-2) were upregulated in both neuron-microglia and neuron-astrocyte co-cultures by LPS. In contrast, neurotrophic factors (brain-derived neurotrophic factor, insulin-like growth factor-1 or glial cell-derived neurotrophic factor) were downregulated in neuron-microglia co-cultures, but upregulated in neuron-astrocyte co-cultures by LPS. IL-10 reduced both the increase in production of the pro-inflammatory mediators and the decrease in production of the neurotrophic factors induced by LPS. These results suggest that astrocytes can balance LPS neurotoxicity by releasing more neurotrophic factors and that IL-10 exerts neuroprotective property by an extensive action including direct on neurons and indirect via inhibiting microglial activation. View Full-Text
Keywords: IL-10; LPS; Parkinson’s disease; dopaminergic neurons; microglia; astrocytes IL-10; LPS; Parkinson’s disease; dopaminergic neurons; microglia; astrocytes
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Zhu, Y.; Chen, X.; Liu, Z.; Peng, Y.-P.; Qiu, Y.-H. Interleukin-10 Protection against Lipopolysaccharide-Induced Neuro-Inflammation and Neurotoxicity in Ventral Mesencephalic Cultures. Int. J. Mol. Sci. 2016, 17, 25.

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