Mesencephalic astrocyte-derived neurotrophic factor attenuates inflammatory responses in lipopolysaccharide-induced neural stem cells by regulating NF-κB and phosphorylation of p38-MAPKs pathways

Abstract

Mesencephalic astrocyte-derived neurotrophic factor (MANF), a new evolutionary conserved neurotrophic factor (NTF), has been reported to protect midbrain dopaminergic neurons of neurodegenerative diseases such as Parkinson’s disease (PD) model. Neural stem cells (NSCs) can play a role as the therapeutic tool in neurodegenerative diseases, but the inflammatory responses of central nervous system (CNS) appear to harm this function. Although studies have previously demonstrated the protective effect of MANF on neurons of CNS, it is lacking in making great efforts on the function of MANF on NSCs. The aim of this study was to investigate the antiinflammatory responses and signaling mechanisms of MANF on lipopolysaccharide (LPS)-induced NSCs. In the results, MANF decreased the proinflammatory cytokines of IL-1β, TNF-α, and IFN-γ induced by LPS by regulating NF-κB and phosphorylation of p38-mitogen-activated protein kinases (MAPKs) pathways, neither p-JNK nor p-ERK signaling. These findings suggest that MANF can facilitate to protect the inflammatory responses of NSCs, and provide beneficial function for the application of NSCs in the therapy.

Keywords:

• Lipopolysaccharide
• MAPK
• mesencephalic astrocyte-derived neurotrophic factor
• neural stem cells
• NF-κB

Acknowledgements

We would like to thank Professor Fei Liu and Dr. Inam Ullah Khan for their reviews on this manuscript.

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Funding information

This study was supported by Grants from the Foundation of Interdisciplinary Center for Human and Social Sciences of Tongji University, National Basic Research of China (973 program 2015cb553706), and National Science and Technology Major Project (2014ZX09102043–003).