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TNF-alpha induces human neural progenitor cell survival after oxygen-glucose deprivation by activating the NF-kappaB pathway

 Miri Kim  ;  Kwangsoo Jung  ;  Il-Sun Kim  ;  Il-Shin Lee  ;  Younhee Ko  ;  Jeong Eun Shin  ;  Kook In Park 
 Experimental and Molecular Medicine, Vol.50(4) : 14, 2018 
Journal Title
 Experimental and Molecular Medicine 
Issue Date
Neural progenitor cell (NPC) transplantation has been shown to be beneficial in the ischemic brain. However, the low survival rate of transplanted NPCs in an ischemic microenvironment limits their therapeutic effects. Tumor necrosis factor-alpha (TNF-alpha) is one of the proinflammatory cytokines involved in the pathogenesis of various injuries. On the other hand, several studies have shown that TNF-alpha influences the proliferation, survival, and differentiation of NPCs. Our study investigated the effect of TNF-alpha pretreatment on human NPCs (hNPCs) under ischemia-related conditions in vitro. hNPCs harvested from fetal brain tissue were pretreated with TNF-alpha before being subjected to oxygen-glucose deprivation (OGD) to mimic ischemia in vitro. TNF-alpha pretreatment improved the viability and reduced the apoptosis of hNPCs after OGD. At the molecular level, TNF-alpha markedly increased the level of NF-kappaB signaling in hNPCs, and an NF-kappaB pathway inhibitor, BAY11-7082, completely reversed the protective effects of TNF-alpha on hNPCs. These results suggest that TNF-alpha improves hNPC survival by activating the NF-kappaB pathway. In addition, TNF-alpha significantly enhanced the expression of cellular inhibitor of apoptosis 2 (cIAP2). Use of a lentivirus-mediated short hairpin RNA targeting cIAP2 mRNA demonstrated that cIAP2 protected against OGD-induced cytotoxicity in hNPCs. Our study of intracellular NF-kappaB signaling revealed that inhibition of NF-kappaB activity abolished the TNF-alpha-mediated upregulation of cIAP2 in hNPCs and blocked TNF-alpha-induced cytoprotection against OGD. Therefore, this study suggests that TNF-alpha pretreatment, which protects hNPCs from OGD-induced apoptosis by activating the NF-kappaB pathway, provides a safe and simple approach to improve the viability of transplanted hNPCs in cerebral ischemia.
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1. College of Medicine (의과대학) > Dept. of Pediatrics (소아청소년과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Il-Sun(김일선) ORCID logo https://orcid.org/0000-0003-4033-4323
Park, Kook In(박국인) ORCID logo https://orcid.org/0000-0001-8499-9293
Shin, Jeong Eun(신정은) ORCID logo https://orcid.org/0000-0002-4376-8541
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