title: 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.
authors.affiliation: a Laboratory of Molecular Medicine, School of Life Sciences and Technology , Tongji University , Shanghai , China ;
authors.forename: Wei
authors.initials: W
authors.lastname: Zhu
authors.affiliation: a Laboratory of Molecular Medicine, School of Life Sciences and Technology , Tongji University , Shanghai , China ;
authors.forename: Jie
authors.initials: J
authors.lastname: Li
authors.affiliation: b Tongji Hospital, Tongji University School of Medicine , Shanghai , China.
authors.forename: Yigang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: a Laboratory of Molecular Medicine, School of Life Sciences and Technology , Tongji University , Shanghai , China ;
authors.forename: Kun
authors.initials: K
authors.lastname: Xie
authors.affiliation: a Laboratory of Molecular Medicine, School of Life Sciences and Technology , Tongji University , Shanghai , China ;
authors.forename: Le
authors.initials: L
authors.lastname: Wang
authors.affiliation: a Laboratory of Molecular Medicine, School of Life Sciences and Technology , Tongji University , Shanghai , China ;
authors.forename: Jianmin
authors.initials: J
authors.lastname: Fang
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D057026:Induced Pluripotent Stem Cells / Q000276:immunology* / Q000473:pathology; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D008070:Lipopolysaccharides / Q000633:toxicity*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D016328:NF-kappa B / Q000276:immunology*; D009414:Nerve Growth Factors / Q000276:immunology*; D058953:Neural Stem Cells / Q000276:immunology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000276:immunology*
chemical_list: D008070:Lipopolysaccharides; C534671:MANF protein, mouse; D016328:NF-kappa B; D009414:Nerve Growth Factors; D048051:p38 Mitogen-Activated Protein Kinases
keywords: Lipopolysaccharide; MAPK; NF-κB; mesencephalic astrocyte-derived neurotrophic factor; neural stem cells