PMID- 25023776
OWN - NLM
STAT- MEDLINE
DCOM- 20150413
LR  - 20190816
IS  - 1878-3279 (Electronic)
IS  - 0171-2985 (Linking)
VI  - 219
IP  - 10
DP  - 2014 Oct
TI  - Unfractionated heparin suppresses lipopolysaccharide-induced monocyte 
      chemoattractant protein-1 expression in human microvascular endothelial cells by 
      blocking Kruppel-like factor 5 and nuclear factor-kappaB pathway.
PG  - 778-85
LID - S0171-2985(14)00102-8 [pii]
LID - 10.1016/j.imbio.2014.06.005 [doi]
AB  - Unfractionated heparin (UFH) and low-molecular-weight heparins (LMWH), apart from 
      anticoagulant activities, contain a variety of biological properties such as 
      anti-inflammatory actions possibly affecting sepsis. Chemokines are vital for 
      promoting the movement of circulating leukocytes to the site of infection and are 
      involved in the pathogenesis of sepsis. The purpose of this study was to 
      investigate the effects and potential mechanisms of UFH on lipopolysaccharide 
      (LPS)-induced chemokine production in human pulmonary microvascular endothelial 
      cells (HPMECs). HPMECs were pretreated with UFH (0.1 U/ml and 1 U/ml), 15 min 
      prior to stimulation with LPS (10 mug/ml). Cells were cultured under various 
      experimental conditions for 2 h and 6 h for analysis. UFH markedly decreased 
      LPS-induced interleukin (IL)-8 and monocyte chemoattractant protein-1 (MCP-1) 
      mRNA and protein expression in HPMECs. UFH also attenuated the secretion of these 
      chemokines in culture supernatants. In addition, UFH blocked the chemotactic 
      activities of LPS-stimulated HPMECs supernatants on monocytes migration as 
      expected. UFH inhibited LPS-induced Kruppel-like factor 5 (KLF-5) mRNA and 
      protein levels. Concurrently, UFH reduced nuclear factor (NF)-kappaB nuclear 
      translocation. Importantly, transfection with siRNA targeting KLF-5 reduced NF-kappaB 
      activation and chemokines expression. These results demonstrate that interfering 
      with KLF-5 mediated NF-kappaB activation might contribute to the inhibitory effects 
      of chemokines and monocytes migration by UFH in LPS-stimulated HPMECs.
CI  - Copyright (c) 2014 Elsevier GmbH. 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 - Li, Xin
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
AD  - Department of Intensive Care Unit, The First Affiliated Hospital, China Medical 
      University, Bei-er Road 92, Shenyang 110001, Liaoning Province, PR China.
FAU - Liu, Yina
AU  - Liu Y
AD  - Department of Intensive Care Unit, The First Affiliated Hospital, China Medical 
      University, Bei-er Road 92, Shenyang 110001, Liaoning Province, PR China.
FAU - Ma, Xiaochun
AU  - Ma X
AD  - Department of Intensive Care Unit, The First Affiliated Hospital, China Medical 
      University, Bei-er Road 92, Shenyang 110001, Liaoning Province, PR China. 
      Electronic address: lx2008yy@gmail.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140630
PL  - Netherlands
TA  - Immunobiology
JT  - Immunobiology
JID - 8002742
RN  - 0 (CCL2 protein, human)
RN  - 0 (CXCL8 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Interleukin-8)
RN  - 0 (KLF5 protein, human)
RN  - 0 (Kruppel-Like Transcription Factors)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-kappa B)
RN  - 9005-49-6 (Heparin)
SB  - IM
MH  - Cell Line
MH  - Cell Movement/drug effects
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Chemokine CCL2/*antagonists & inhibitors/metabolism
MH  - Endothelial Cells/*drug effects/metabolism
MH  - Heparin/*pharmacology
MH  - Humans
MH  - Interleukin-8/metabolism
MH  - Kruppel-Like Transcription Factors/*antagonists & inhibitors/genetics/metabolism
MH  - Lipopolysaccharides
MH  - Monocytes/drug effects/physiology
MH  - NF-kappa B/*antagonists & inhibitors/metabolism
OTO - NOTNLM
OT  - Endothelial cells
OT  - Kruppel-like factor 5
OT  - Monocyte chemoattractant protein-1
OT  - Nuclear factor-kappaB
OT  - Sepsis
OT  - Unfractionated heparin
EDAT- 2014/07/16 06:00
MHDA- 2015/04/14 06:00
CRDT- 2014/07/16 06:00
PHST- 2014/04/08 00:00 [received]
PHST- 2014/06/24 00:00 [accepted]
PHST- 2014/07/16 06:00 [entrez]
PHST- 2014/07/16 06:00 [pubmed]
PHST- 2015/04/14 06:00 [medline]
AID - S0171-2985(14)00102-8 [pii]
AID - 10.1016/j.imbio.2014.06.005 [doi]
PST - ppublish
SO  - Immunobiology. 2014 Oct;219(10):778-85. doi: 10.1016/j.imbio.2014.06.005. Epub 
      2014 Jun 30.