PMID- 29622770
OWN - NLM
STAT- MEDLINE
DCOM- 20190211
LR  - 20210227
IS  - 2092-6413 (Electronic)
IS  - 1226-3613 (Print)
IS  - 1226-3613 (Linking)
VI  - 50
IP  - 4
DP  - 2018 Apr 6
TI  - TNF-alpha induces human neural progenitor cell survival after oxygen-glucose 
      deprivation by activating the NF-kappaB pathway.
PG  - 1-14
LID - 10.1038/s12276-018-0033-1 [doi]
LID - 14
AB  - 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.
FAU - Kim, Miri
AU  - Kim M
AD  - Brain Korea 21 Plus Project for Medical Science, Yonsei University College of 
      Medicine, Seoul, 03722, Korea.
FAU - Jung, Kwangsoo
AU  - Jung K
AD  - Yonsei Biomedical Research Institute, Yonsei University College of Medicine, 
      Seoul, 03722, Korea.
FAU - Kim, Il-Sun
AU  - Kim IS
AD  - Yonsei Biomedical Research Institute, Yonsei University College of Medicine, 
      Seoul, 03722, Korea.
FAU - Lee, Il-Shin
AU  - Lee IS
AD  - Yonsei Biomedical Research Institute, Yonsei University College of Medicine, 
      Seoul, 03722, Korea.
FAU - Ko, Younhee
AU  - Ko Y
AD  - Division of Biomedical Engineering, Hankuk University of Foreign Studies, Yongin, 
      17035, Korea.
FAU - Shin, Jeong Eun
AU  - Shin JE
AD  - Department of Pediatrics, Severance Children's Hospital, Yonsei University 
      College of Medicine, Seoul, 03722, Korea.
FAU - Park, Kook In
AU  - Park KI
AD  - Brain Korea 21 Plus Project for Medical Science, Yonsei University College of 
      Medicine, Seoul, 03722, Korea. kipark@yuhs.ac.
AD  - Yonsei Biomedical Research Institute, Yonsei University College of Medicine, 
      Seoul, 03722, Korea. kipark@yuhs.ac.
AD  - Department of Pediatrics, Severance Children's Hospital, Yonsei University 
      College of Medicine, Seoul, 03722, Korea. kipark@yuhs.ac.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180406
PL  - United States
TA  - Exp Mol Med
JT  - Experimental & molecular medicine
JID - 9607880
RN  - 0 (NF-kappa B)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.3.2.27 (Baculoviral IAP Repeat-Containing 3 Protein)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - IY9XDZ35W2 (Glucose)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Baculoviral IAP Repeat-Containing 3 Protein/genetics/metabolism
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Glucose/*metabolism
MH  - Humans
MH  - NF-kappa B/*metabolism
MH  - Neoplastic Stem Cells/drug effects/*metabolism
MH  - Oxygen/*metabolism
MH  - Signal Transduction/*drug effects
MH  - Tumor Necrosis Factor-alpha/*metabolism/pharmacology
MH  - p38 Mitogen-Activated Protein Kinases
PMC - PMC5938012
COIS- The authors declare that they have no conflict of interest.
EDAT- 2018/04/07 06:00
MHDA- 2019/02/12 06:00
PMCR- 2018/04/06
CRDT- 2018/04/07 06:00
PHST- 2017/05/27 00:00 [received]
PHST- 2017/12/05 00:00 [accepted]
PHST- 2017/11/14 00:00 [revised]
PHST- 2018/04/07 06:00 [entrez]
PHST- 2018/04/07 06:00 [pubmed]
PHST- 2019/02/12 06:00 [medline]
PHST- 2018/04/06 00:00 [pmc-release]
AID - 10.1038/s12276-018-0033-1 [pii]
AID - 33 [pii]
AID - 10.1038/s12276-018-0033-1 [doi]
PST - epublish
SO  - Exp Mol Med. 2018 Apr 6;50(4):1-14. doi: 10.1038/s12276-018-0033-1.