PMID- 22119392
OWN - NLM
STAT- MEDLINE
DCOM- 20120723
LR  - 20120319
IS  - 1879-2472 (Electronic)
IS  - 0049-3848 (Linking)
VI  - 129
IP  - 4
DP  - 2012 Apr
TI  - BMP-2 inhibits TF expression in human monocytes by shutting down MAPK signaling 
      and AP-1 transcriptional activity.
PG  - e106-11
LID - 10.1016/j.thromres.2011.10.024 [doi]
AB  - 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.
CI  - Copyright (c) 2011 Elsevier Ltd. All rights reserved.
FAU - Egorina, E M
AU  - Egorina EM
AD  - Hematological Research Group, Faculty of Health Sciences, University of Tromso, 
      9037, Tromso, Norway.
FAU - Sovershaev, T A
AU  - Sovershaev TA
FAU - Hansen, J B
AU  - Hansen JB
FAU - Sovershaev, M A
AU  - Sovershaev MA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20111125
PL  - United States
TA  - Thromb Res
JT  - Thrombosis research
JID - 0326377
RN  - 0 (BMP2 protein, human)
RN  - 0 (Bone Morphogenetic Protein 2)
RN  - 0 (NF-kappa B)
RN  - 0 (Transcription Factor AP-1)
RN  - 9035-58-9 (Thromboplastin)
SB  - IM
MH  - Bone Morphogenetic Protein 2/*pharmacokinetics
MH  - Cells, Cultured
MH  - Down-Regulation/drug effects
MH  - Humans
MH  - MAP Kinase Signaling System/drug effects/*physiology
MH  - Monocytes/*metabolism
MH  - NF-kappa B/*metabolism
MH  - Thromboplastin/*metabolism
MH  - Transcription Factor AP-1/*metabolism
MH  - Transcriptional Activation/drug effects/*physiology
EDAT- 2011/11/29 06:00
MHDA- 2012/07/24 06:00
CRDT- 2011/11/29 06:00
PHST- 2011/07/26 00:00 [received]
PHST- 2011/10/11 00:00 [revised]
PHST- 2011/10/24 00:00 [accepted]
PHST- 2011/11/29 06:00 [entrez]
PHST- 2011/11/29 06:00 [pubmed]
PHST- 2012/07/24 06:00 [medline]
AID - S0049-3848(11)00564-0 [pii]
AID - 10.1016/j.thromres.2011.10.024 [doi]
PST - ppublish
SO  - Thromb Res. 2012 Apr;129(4):e106-11. doi: 10.1016/j.thromres.2011.10.024. Epub 
      2011 Nov 25.