PMID- 25738414 OWN - NLM STAT- MEDLINE DCOM- 20160105 LR - 20181202 IS - 1791-3004 (Electronic) IS - 1791-2997 (Linking) VI - 12 IP - 1 DP - 2015 Jul TI - Co-culture with bone marrow stromal cells protects PC12 neuronal cells from tumor necrosis factor-alpha-induced apoptosis by inhibiting the tumor necrosis factor receptor/caspase signaling pathway. PG - 261-6 LID - 10.3892/mmr.2015.3421 [doi] AB - Bone marrow stromal cells (BMSCs), derived from the mesoderm, have been applied in the repair and reconstruction of injured tissues. The present study was conducted to explore the effects of BMSCs on cell viability of tumor necrosis factor-alpha (TNF-alpha)-stimulated PC12 cells. PC12 cells were co-cultured with BMSCs under TNF-alpha treatment, with normal PC12 cells as controls. Results from an MTT assay indicated that BMSCs significantly increased cell growth and proliferation of TNF-alpha-treated PC12 cells (survival rates were 56.71 and 76.86% for the positive control (PC) and co-culture group, respectively). Furthermore, Annexin V/propidium iodide staining and flow cytometric analysis demonstrated that TNF-alpha increased PC12-cell apoptosis from 3.49 to 40.74% in the negative control and PC group, and the apoptotic rate was significantly reduced upon co-culture with BMSCs to 16.97%. In addition, data from reverse transcription-quantitative polymerase chain reaction and western blot analyses illustrated that TNF-alpha-induced upregulation in TNF receptor (TNFR)-1 (TNFR1) and caspase-8 expression in PC12 cells were partially reversed by co-culture with BMSCs. In conclusion, the present study suggested that BMSCs protect PC12 cells against stimulation with TNF-alpha, which is partially mediated through the TNFR/caspase signaling pathway. The results of the present study also suggested a therapeutic use of BMSCs in clinical neurodegenerative diseases. FAU - Li, Li AU - Li L AD - Department of Neurology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China. FAU - Wang, Jing AU - Wang J AD - Department of Neurology, The 463th Hospital of the Chinese People's Liberation Army, Shenyang, Liaoning 110042, P.R. China. FAU - Tang, Ling AU - Tang L AD - Department of Neurology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China. FAU - Yu, Xin AU - Yu X AD - Department of Clinical Pharmacy, China Medical University, Shenyang, Liaoning 110001, P.R. China. FAU - Sui, Yi AU - Sui Y AD - Department of Neurology, Shenyang First People's Hospital, Shenyang, Liaoning 110041, P.R. China. FAU - Zhang, Chaodong AU - Zhang C AD - Department of Neurology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China. LA - eng PT - Journal Article DEP - 20150304 PL - Greece TA - Mol Med Rep JT - Molecular medicine reports JID - 101475259 RN - 0 (Annexin A5) RN - 0 (Receptors, Tumor Necrosis Factor, Type I) RN - 0 (Tnfrsf1a protein, rat) RN - 0 (Tumor Necrosis Factor-alpha) RN - 36015-30-2 (Propidium) RN - EC 3.4.22.- (Casp8 protein, rat) RN - EC 3.4.22.- (Caspase 8) SB - IM MH - Animals MH - Annexin A5 MH - Apoptosis/drug effects MH - Bone Marrow Cells/cytology/*drug effects/immunology MH - Caspase 8/*genetics/metabolism MH - Cell Communication MH - Cell Differentiation MH - Coculture Techniques MH - Gene Expression Regulation MH - Humans MH - Mesenchymal Stem Cells/cytology/*drug effects/immunology MH - Neurons/cytology/*drug effects/immunology MH - PC12 Cells MH - Propidium MH - Rats MH - Rats, Sprague-Dawley MH - Receptors, Tumor Necrosis Factor, Type I/antagonists & inhibitors/*genetics/metabolism MH - Signal Transduction MH - Tumor Necrosis Factor-alpha/*pharmacology EDAT- 2015/03/05 06:00 MHDA- 2016/01/06 06:00 CRDT- 2015/03/05 06:00 PHST- 2014/04/17 00:00 [received] PHST- 2015/01/02 00:00 [accepted] PHST- 2015/03/05 06:00 [entrez] PHST- 2015/03/05 06:00 [pubmed] PHST- 2016/01/06 06:00 [medline] AID - 10.3892/mmr.2015.3421 [doi] PST - ppublish SO - Mol Med Rep. 2015 Jul;12(1):261-6. doi: 10.3892/mmr.2015.3421. Epub 2015 Mar 4.