title: BMP-2 inhibits TF expression in human monocytes by shutting down MAPK signaling and AP-1 transcriptional activity.
abstract: BACKGROUND
  We have recently identified bone morphogenetic protein (BMP)-2 as a novel inhibitor of tissue factor (TF) expression in lipopolysaccharide (LPS)-activated human monocytes, and now sought for intracellular mechanisms.
  
  
  METHODS
  Here, we studied activation status of mitogen activated protein kinases (MAPKs) extracellular signal-regulated protein kinase (Erk) 1/2, p38, and c-Jun N-terminal kinase (JNK) as well as transcription factors activator protein (AP)-1 and nuclear factor kappa B (NF-kB), which regulate inducible expression of TF.
  
  
  RESULTS
  Human mononuclear cells (MNCs) responded to BMP-2 stimulation with activation of canonic Smad1/5/8 signaling. Pretreatment with BMP-2 prevented LPS-induced increase in surface presentation, intracellular accumulation, and fraction of TF-positive MNCs. Similarly, LPS-induced increase in levels of phosphorylated Erk1/2, p38, and JNK was markedly diminished by BMP-2 pretreatment. BMP-2 pretreatment prior to LPS significantly diminished LPS-induced transcriptional activation of AP-1-dependent reporter. In contrast, BMP-2 given prior to LPS did not dampen the transcriptional activation of NF-kB-sensitive luciferase reporter.
  
  
  CONCLUSIONS
  BMP-2 can inhibit LPS-induced TF protein expression and surface presentation in human MNCs by downregulation of Erk1/2, p38, and JNK signaling, as well as reduced transcriptional activity of AP-1, but not NF-kB.
authors: Hematological Research Group, Faculty of Health Sciences, University of Tromsø, 9037, Tromsø, Norway.
authors: E M
authors: EM
authors: Egorina
authors: T A
authors: TA
authors: Sovershaev
authors: J B
authors: JB
authors: Hansen
authors: M A
authors: MA
authors: Sovershaev
mesh_terms: D055396:Bone Morphogenetic Protein 2 / Q000493:pharmacokinetics*; D002478:Cells, Cultured; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D009000:Monocytes / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D013925:Thromboplastin / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects / Q000502:physiology*
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D016328:NF-kappa B; D018808:Transcription Factor AP-1; D013925:Thromboplastin