title: IL-6 regulates stress-induced REX-1 expression via ATP-P2Y1 signalling in stem cells isolated from human exfoliated deciduous teeth.
abstract: OBJECTIVE
  To investigate the relationship between ATP and IL-6 in mechanical stress-induced REX-1 expression in SHEDs.
  
  
  METHODS
  Cells were stimulated with mechanical stress (0-2.5 gcm(-2)), IL-6 (0.1-5 ng/ml), or ATP (10-100 μM) for 2h in serum-free media. IL-6 and REX-1 expression was examined by qualitative and quantitative polymerase chain reaction. ATP release was measured using a bioluminescence assay. The molecular mechanisms of the signalling pathways were investigated using chemical inhibitors.
  
  
  RESULTS
  Mechanical stress induced IL-6 and REX-1 mRNA expression and ATP release. JAK inhibitor I inhibited the increase in REX-1 expression and ATP release but not IL-6 induction. Furthermore, suramin inhibited the upregulation of REX-1 mRNA expression but not ATP release. Exogenous IL-6 promoted both ATP release and REX-1 expression. The IL-6-induced REX-1 expression was attenuated by a P2Y1-specific receptor antagonist. Moreover, REX-1 expression was upregulated in a dose-dependent manner by the addition of ATP or a P2Y1 agonist. This inductive effect was abolished by the P2Y1-specific receptor antagonist.
  
  
  CONCLUSIONS
  ATP-P2Y1 signalling is involved in IL-6-regulated stress-induced REX-1 expression in SHEDs. These results imply the participation of mechanical stress, IL-6, and ATP in regulating the expression of REX-1, a pluripotent stem cell marker.
authors.affiliation: Research Unit of Mineralized Tissue, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand; Graduate Program in Oral Biology, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand. Electronic address: nattanang@gmail.com.
authors.forename: Nattanan
authors.initials: N
authors.lastname: Govitvattana
authors.affiliation: Research Unit of Mineralized Tissue, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand; Department of Anatomy, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand. Electronic address: osathanon.t@gmail.com.
authors.forename: Thanaphum
authors.initials: T
authors.lastname: Osathanon
authors.affiliation: Department of Mental Health, Ministry of Public Health, Bangkok, Thailand. Electronic address: nongraja@hotmail.com.
authors.forename: Thasanporn
authors.initials: T
authors.lastname: Toemthong
authors.affiliation: Research Unit of Mineralized Tissue, Faculty of Dentistry, Chulalongkorn University, Bangkok, Thailand. Electronic address: prasit215@gmail.com.
authors.forename: Prasit
authors.initials: P
authors.lastname: Pavasant
mesh_terms: D000255:Adenosine Triphosphate / Q000502:physiology*; D001696:Biomechanical Phenomena; D006801:Humans; D015850:Interleukin-6 / Q000502:physiology*; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism*; D008163:Luminescent Measurements; D040542:Mechanotransduction, Cellular / Q000502:physiology; D059630:Mesenchymal Stem Cells / Q000502:physiology; D058912:Purinergic P2Y Receptor Agonists / Q000494:pharmacology; D058921:Purinergic P2Y Receptor Antagonists / Q000494:pharmacology; D058470:Receptors, Purinergic P2Y / Q000187:drug effects / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013314:Stress, Mechanical; D014094:Tooth, Deciduous / Q000166:cytology*; D015854:Up-Regulation
chemical_list: D015850:Interleukin-6; D051741:Kruppel-Like Transcription Factors; D058912:Purinergic P2Y Receptor Agonists; D058921:Purinergic P2Y Receptor Antagonists; D058470:Receptors, Purinergic P2Y; C507976:ZFP42 protein, human; D000255:Adenosine Triphosphate
keywords: ATP; IL-6; P2Y1; Rex-1; SHEDs; Stemness