Paroxetine ameliorates lipopolysaccharide-induced microglia activation via differential regulation of MAPK signaling

Journal of Neuroinflammation

Jian-Hong Zhu¹  Xiong Zhang²  Song-Fang Chen²  Li-Li Zhou²  Jun-Mei Lai²  Juan-Juan Zhu²  Jian-Yong Wang²  Ming Zou²  Rong-Pei Liu² 

[1]Department of Preventive Medicine, Wenzhou Medical University, Wenzhou, Zhejiang 325035, China

[2]Department of Neurology & Geriatrics, the Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang 325000, China

关键词: MAPK;    Neuroinflammation;    Lipopolysaccharide;    Microglia;    Paroxetine;   

Others  :  812039
DOI  :  10.1186/1742-2094-11-47

 received in 2013-09-10, accepted in 2014-02-24,  发布年份 2014

【 摘 要 】

Background

Paroxetine, a selective serotonin reuptake inhibitor for counteracting depression, has been recently suggested as having a role in prevention of dopaminergic neuronal degeneration in substantia nigra, a hallmark of Parkinson’s disease (PD). The pathogenesis of this type of neurological disorders often involves the activation of microglia and associated inflammatory processes. Thus in this study we aimed to understand the role of paroxetine in microglia activation and to elucidate the underlying mechanism(s).

Methods

BV2 and primary microglial cells were pretreated with paroxetine and stimulated with lipopolysaccharide (LPS). Cells were assessed for the responses of pro-inflammatory mediator and cytokines, and the related signaling pathways were evaluated and analyzed in BV2 cells.

Results

Paroxetine significantly inhibited LPS-induced production of nitric oxide (NO) and pro-inflammatory cytokines such as TNF-α and IL-1β. Further analysis showed inducible nitric oxide synthase (iNOS) and mRNA expression of TNF-α and IL-1β were attenuated by paroxetine pretreatment. Analyses in signaling pathways demonstrated that paroxetine led to suppression of LPS-induced JNK1/2 activation and baseline ERK1/2 activity, but had little effect on the activation of p38 and p65/NF-κB. Interference with specific inhibitors revealed that paroxetine-mediated suppression of NO production was via JNK1/2 pathway while the cytokine suppression was via both JNK1/2 and ERK1/2 pathways. Furthermore, conditioned media culture showed that paroxetine suppressed the microglia-mediated neurotoxicity.

Conclusions

Paroxetine inhibits LPS-stimulated microglia activation through collective regulation of JNK1/2 and ERK1/2 signaling. Our results indicate a potential role of paroxetine in neuroprotection via its anti-neuroinflammatory effect besides targeting for depression.

【 授权许可】

   
2014 Liu et al.; licensee BioMed Central Ltd.

【 图 表 】

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