PMID- 30016181
OWN - NLM
STAT- MEDLINE
DCOM- 20191017
LR  - 20191017
IS  - 1557-7465 (Electronic)
IS  - 1079-9907 (Linking)
VI  - 38
IP  - 7
DP  - 2018 Jul
TI  - Unfractionated Heparin Modulates Lipopolysaccharide-Induced Cytokine Production 
      by Different Signaling Pathways in THP-1 Cells.
PG  - 283-289
LID - 10.1089/jir.2018.0042 [doi]
AB  - Sepsis is a complex syndrome resulting from the innate host response to 
      infection. Apart from the well-known anticoagulant effects of heparin, it also 
      possesses various immunomodulatory properties. Thus heparin seems to be a 
      therapeutic drug in sepsis. We have demonstrated that unfractionated heparin 
      (UFH) can inhibit lipopolysaccharide (LPS)-induced inflammatory responses in 
      endothelial cells. The monocyte/macrophage system is a major contributor to host 
      immunity and immune surveillance against infection. The aim of the study is to 
      determine the inhibitory effect of UFH on cytokine production in THP-1 monocytes 
      induced by LPS and to define the possible signaling pathways. The THP-1 cells 
      were treated with UFH (0.1-10 U/mL) for 15 min before exposure to LPS 
      (100 ng/mL). After 1 h, nuclear factor-kappaB (NF-kappaB) and phosphorylated inhibitor 
      kappaB-alpha (IkappaB-alpha), c-Jun, c-fos, ERK1/2, JNK, and p38 mitogen-activated protein kinase 
      (MAPK) expression levels were evaluated by Western blot. After 6 h, interleukin 
      (IL)-1beta, tumor necrosis factor-alpha (TNF-alpha), IL-6, IL-8, and IL-18 protein 
      concentrations were measured by enzyme-linked immunosorbent assay. Cell viability 
      was determined by methyl thiazoyltetrazolium (MTT) assay. UFH inhibited 
      LPS-induced phosphorylation of IkappaB-alpha, c-Jun, ERK1/2, JNK, and p38 MAPK but not 
      c-fos. UFH also suppressed LPS-induced nuclear translocation of NF-kappaB. As 
      expected, UFH decreased LPS-induced IL-1beta, TNF-alpha, IL-6, IL-8, and IL-18 protein 
      levels, suggesting that UFH has an anti-inflammatory effect on THP-1 cells by 
      interrupting the MAPK, NF-kappaB, and c-Jun signaling pathways. UFH could potentially 
      contribute to treatments for sepsis.
FAU - Li, Xu
AU  - Li X
AD  - Department of Intensive Care Unit, The First Affiliated Hospital, China Medical 
      University , Shenyang, P.R. China .
FAU - Zhao, Enfang
AU  - Zhao E
AD  - Department of Intensive Care Unit, The First Affiliated Hospital, China Medical 
      University , Shenyang, P.R. China .
FAU - Li, Lu
AU  - Li L
AD  - Department of Intensive Care Unit, The First Affiliated Hospital, China Medical 
      University , Shenyang, P.R. China .
FAU - Ma, Xiaochun
AU  - Ma X
AD  - Department of Intensive Care Unit, The First Affiliated Hospital, China Medical 
      University , Shenyang, P.R. China .
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Interferon Cytokine Res
JT  - Journal of interferon & cytokine research : the official journal of the 
      International Society for Interferon and Cytokine Research
JID - 9507088
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (Cytokines)
RN  - 0 (Lipopolysaccharides)
RN  - 9005-49-6 (Heparin)
SB  - IM
MH  - Anti-Inflammatory Agents, Non-Steroidal/pharmacology
MH  - Cell Survival/drug effects
MH  - Cytokines/*biosynthesis/immunology
MH  - Heparin/*pharmacology
MH  - Humans
MH  - Lipopolysaccharides/*immunology
MH  - Sepsis/drug therapy/immunology
MH  - Signal Transduction/*drug effects
MH  - THP-1 Cells
OTO - NOTNLM
OT  - THP-1 cells
OT  - cytokine
OT  - mitogen-activated protein kinase
OT  - nuclear factor-kappaB
OT  - unfractionated heparin
EDAT- 2018/07/18 06:00
MHDA- 2019/10/18 06:00
CRDT- 2018/07/18 06:00
PHST- 2018/07/18 06:00 [entrez]
PHST- 2018/07/18 06:00 [pubmed]
PHST- 2019/10/18 06:00 [medline]
AID - 10.1089/jir.2018.0042 [doi]
PST - ppublish
SO  - J Interferon Cytokine Res. 2018 Jul;38(7):283-289. doi: 10.1089/jir.2018.0042.