PMID- 22763042
OWN - NLM
STAT- MEDLINE
DCOM- 20130201
LR  - 20161125
IS  - 1096-0023 (Electronic)
IS  - 1043-4666 (Linking)
VI  - 60
IP  - 1
DP  - 2012 Oct
TI  - Unfractionated heparin inhibits lipopolysaccharide-induced inflammatory response 
      through blocking p38 MAPK and NF-kappaB activation on endothelial cell.
PG  - 114-21
LID - 10.1016/j.cyto.2012.06.008 [doi]
AB  - Heparins, including unfractionated heparin (UFH) and low-molecular-weight 
      heparins (LMWH), are glycosaminoglycans that are largely used as anti-thrombotic 
      drugs. While the mechanisms of their anticoagulant actions in blood have been 
      extensively studied, their effects on the inflammation of the endothelium are 
      still under investigation since the endothelium plays a central role in sepsis. 
      Furthermore, UFH is much cheaper than LMWH. The aim of this study was to 
      determine how UFH regulates lipopolysaccharide (LPS)-induced inflammatory 
      response on endothelial cells in vitro, and define the role of p38 
      mitogen-activated protein kinase (MAPK) and nuclear factor-kappaB (NF-kappaB) in 
      mediating this effect. Human pulmonary microvascular endothelial cells (HPMECs) 
      were pretreated with UFH (0.01 U/ml-10 U/ml), prior to stimulation with LPS (10 
      mug/ml). Markers of systemic inflammation and endothelial activation were 
      assessed. Interleukin (IL)-1beta, IL-6, E-selectin, intercellular adhesion molecule 
      (ICAM)-1 release were subsequently measured at 2h, 6h and 12h. Phosphorylation of 
      p38 MAPK at 2h, 6h and nuclear translocation of the proinflammatory NF-kappaB at 2h 
      were assessed. In HPMEC, UFH significantly attenuated LPS-induced production of 
      IL-1beta, IL-6, E-selectin and ICAM-1, as well as phosphorylation of p38 MAPK and 
      NF-kappaB translocation, especially in 10 U/ml. In conclusion, UFH at high dose 
      significantly protects against endothelial-cell-mediated immune response. The 
      inhibition of p38 MAPK and NF-kappaB activation certainly represents one of the 
      mechanisms by which UFH exerts its anti-inflammatory effect.
CI  - Copyright (c) 2012 Elsevier Ltd. All rights reserved.
FAU - Li, Xu
AU  - Li X
AD  - Department of Intensive Care Unit, The First Affiliated Hospital, China Medical 
      University, Bei-er Road 92, Shenyang 110001, Liaoning Province, PR China.
FAU - Zheng, Zhen
AU  - Zheng Z
FAU - Li, Xin
AU  - Li X
FAU - Ma, Xiaochun
AU  - Ma X
LA  - eng
PT  - Journal Article
DEP - 20120702
PL  - England
TA  - Cytokine
JT  - Cytokine
JID - 9005353
RN  - 0 (Cytokines)
RN  - 0 (E-Selectin)
RN  - 0 (I-kappa B Proteins)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Interleukin-6)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NFKBIA protein, human)
RN  - 0 (Transcription Factor RelA)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - 139874-52-5 (NF-KappaB Inhibitor alpha)
RN  - 9005-49-6 (Heparin)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Active Transport, Cell Nucleus/drug effects
MH  - Blotting, Western
MH  - Cell Nucleus/metabolism
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Cytokines/genetics/metabolism
MH  - E-Selectin/genetics/metabolism
MH  - Endothelial Cells/*drug effects/metabolism
MH  - Gene Expression/drug effects
MH  - Heparin/*pharmacology
MH  - Humans
MH  - I-kappa B Proteins/metabolism
MH  - Inflammation Mediators/*metabolism
MH  - Intercellular Adhesion Molecule-1/genetics/metabolism
MH  - Interleukin-1beta/genetics/metabolism
MH  - Interleukin-6/genetics/metabolism
MH  - Lipopolysaccharides/*pharmacology
MH  - Lung/blood supply
MH  - Microvessels/cytology
MH  - NF-KappaB Inhibitor alpha
MH  - Phosphorylation/drug effects
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Transcription Factor RelA/*metabolism
MH  - p38 Mitogen-Activated Protein Kinases/*metabolism
EDAT- 2012/07/06 06:00
MHDA- 2013/02/05 06:00
CRDT- 2012/07/06 06:00
PHST- 2011/08/31 00:00 [received]
PHST- 2012/05/29 00:00 [revised]
PHST- 2012/06/04 00:00 [accepted]
PHST- 2012/07/06 06:00 [entrez]
PHST- 2012/07/06 06:00 [pubmed]
PHST- 2013/02/05 06:00 [medline]
AID - S1043-4666(12)00253-0 [pii]
AID - 10.1016/j.cyto.2012.06.008 [doi]
PST - ppublish
SO  - Cytokine. 2012 Oct;60(1):114-21. doi: 10.1016/j.cyto.2012.06.008. Epub 2012 Jul 
      2.