Stimulation of EphB2/ephrin-B1 signalling by tumour necrosis factor alpha in human dental pulp stem cells

Cell Prolif. 2015 Apr;48(2):231-8. doi: 10.1111/cpr.12172. Epub 2015 Feb 3.

Abstract

Objectives: The aim of this study was to investigate whether in vitro stimulation of dental pulp stem cells (DPSCs) by tumour necrosis factor alpha (TNF-α) would induce secretion of EphB2/ephrin-B1 signalling.

Materials and methods: Dental pulp stem cells isolated from human dental pulp were treated with TNF-α (5-100 ng/ml) over 2-48 h. EphB2/ephrin-B1 mRNA and protein levels were measured by real-time polymerase chain reaction (RT-PCR) and western blot analysis respectively. Additionally, DPSCs were pre-incubated with TNF-α receptor neutralizing antibodies or infected with nuclear factor-kappa B (NF-ĸB) inhibitor, p38 MAPK inhibitor, Jun N-terminal kinase (JNK) inhibitor and MEK inhibitor before TNF-α treatment. Results were analysed by one-way ANOVA.

Results: Tumour necrosis factor alpha increased EphB2 mRNA expression in DPSCs at concentrations up to 20 ng/ml and ephrin-B1 at concentrations up to 40 ng/ml (P < 0.05). Its mRNA expression reached maximum at 24 h when treated with TNF-α at 20 ng/ml (P < 0.05). EphB2/ephrin-B1 protein expression levels were high at 16 and 24 h as shown by western blotting. Neutralizing antibodies for TNFR1/2 receptors down-regulated EphB2/ephrin-B1 mRNA expression (P < 0.05) and ephrin-B1 protein expression, but not EphB2 protein expression. JNK-inhibitor inhibited EphB2 mRNA expression only (P < 0.05).

Conclusions: EphB2/ephrin-B1 were invoked in DPSCs with TNF-α treatment via the JNK-dependent pathway, but not NF-ĸB, p38 MAPK or MEK signalling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antibodies / immunology
  • Cells, Cultured
  • Dental Pulp / cytology*
  • Ephrin-B1 / genetics
  • Ephrin-B1 / metabolism*
  • Humans
  • JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • MAP Kinase Signaling System
  • Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors
  • NF-kappa B / antagonists & inhibitors
  • Receptor, EphB2 / genetics
  • Receptor, EphB2 / metabolism*
  • Receptors, Tumor Necrosis Factor, Type I / metabolism
  • Receptors, Tumor Necrosis Factor, Type II / metabolism
  • Stem Cells / cytology*
  • Tumor Necrosis Factor-alpha / immunology
  • Tumor Necrosis Factor-alpha / pharmacology*
  • Young Adult
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors

Substances

  • Antibodies
  • EFNB1 protein, human
  • Ephrin-B1
  • NF-kappa B
  • Receptors, Tumor Necrosis Factor, Type I
  • Receptors, Tumor Necrosis Factor, Type II
  • TNFRSF1A protein, human
  • TNFRSF1B protein, human
  • Tumor Necrosis Factor-alpha
  • EPHB2 protein, human
  • Receptor, EphB2
  • JNK Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinase Kinases