PMID- 32063752
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220412
IS  - 1476-9255 (Print)
IS  - 1476-9255 (Electronic)
IS  - 1476-9255 (Linking)
VI  - 17
DP  - 2020
TI  - Different signaling pathways involved in the anti-inflammatory effects of 
      unfractionated heparin on lipopolysaccharide-stimulated human endothelial cells.
PG  - 5
LID - 10.1186/s12950-020-0238-7 [doi]
LID - 5
AB  - BACKGROUND: There is a complex interplay between inflammatory response and 
      coagulation in sepsis. Heparin is used as a recognized anticoagulant and 
      possesses multiple biological properties that possibly affect sepsis. This study 
      aimed to determine the possible signaling pathways involved in the 
      anti-inflammatory effects of unfractionated heparin (UFH) on lipopolysaccharide 
      (LPS)-stimulated human pulmonary microvascular endothelial cells (HPMECs). 
      METHODS: HPMECs were transfected with siRNA targeting IkappaB-alpha. Cells were treated 
      with UFH (0.01 U/ml~ 10 U/ml) 15 min before adding LPS (10 mug/ml). We detected 
      the markers of systemic inflammatory response. Release of interleukin (IL)-6, 
      IL-8 were evaluated at 3 h by ELISA and at 1 h by qRT-PCR. After 1 h, nuclear 
      factor-kappaB (NF-kappaB) as well as phosphorylated inhibitor kappaB-alpha (IkappaB-alpha), signal 
      transducer and activator of transcription-3 (STAT3) and ERK1/2, JNK, p38 
      mitogen-activated protein kinase (MAPK) expressions were evaluated by Western 
      blot. DNA binding was conducted to further prove the activation of NF-kappaB pathway. 
      RESULTS: In HPMECs, UFH obviously inhibited LPS-stimulated production of IL-6 and 
      IL-8, especially in 10 U/ml. UFH inhibited LPS-induced phosphorylation of IkappaB-alpha, 
      ERK1/2, JNK, p38 MAPK and STAT3. UFH also suppressed LPS-stimulated nuclear 
      translocation of NF-kappaB. Importantly, transfection with siRNA targeting IkappaB-alpha 
      induced more obvious inflammatory response. UFH suppressed cytokines production 
      and phosphorylation of different signaling pathways in IkappaB-alpha silencing cells. 
      CONCLUSION: These results demonstrate that UFH exerts the anti-inflammatory 
      effects on LPS-stimulated HPMECs by different signaling pathways.
CI  - (c) The Author(s). 2020.
FAU - Li, Xu
AU  - Li X
AUID- ORCID: 0000-0001-6750-9539
AD  - Department of Critical Care Medicine, the First Affiliated Hospital, China 
      Medical University, North Nanjing Street 155, Shenyang, 110001 Liaoning Province 
      People's Republic of China. GRID: grid.412449.e. ISNI: 0000 0000 9678 1884
FAU - Li, Lu
AU  - Li L
AD  - Department of Critical Care Medicine, the First Affiliated Hospital, China 
      Medical University, North Nanjing Street 155, Shenyang, 110001 Liaoning Province 
      People's Republic of China. GRID: grid.412449.e. ISNI: 0000 0000 9678 1884
FAU - Shi, Yuequan
AU  - Shi Y
AD  - Department of Critical Care Medicine, the First Affiliated Hospital, China 
      Medical University, North Nanjing Street 155, Shenyang, 110001 Liaoning Province 
      People's Republic of China. GRID: grid.412449.e. ISNI: 0000 0000 9678 1884
FAU - Yu, Sihan
AU  - Yu S
AD  - Department of Critical Care Medicine, the First Affiliated Hospital, China 
      Medical University, North Nanjing Street 155, Shenyang, 110001 Liaoning Province 
      People's Republic of China. GRID: grid.412449.e. ISNI: 0000 0000 9678 1884
FAU - Ma, Xiaochun
AU  - Ma X
AD  - Department of Critical Care Medicine, the First Affiliated Hospital, China 
      Medical University, North Nanjing Street 155, Shenyang, 110001 Liaoning Province 
      People's Republic of China. GRID: grid.412449.e. ISNI: 0000 0000 9678 1884
LA  - eng
PT  - Journal Article
DEP - 20200210
PL  - England
TA  - J Inflamm (Lond)
JT  - Journal of inflammation (London, England)
JID - 101232234
PMC - PMC7011532
OTO - NOTNLM
OT  - Endothelial cells
OT  - Nuclear factor-kappaB
OT  - Sepsis
OT  - Signaling pathway
OT  - Unfractionated heparin
COIS- Competing interestsThe authors declare that they have no competing interests.
EDAT- 2020/02/18 06:00
MHDA- 2020/02/18 06:01
PMCR- 2020/02/10
CRDT- 2020/02/18 06:00
PHST- 2019/11/12 00:00 [received]
PHST- 2020/01/27 00:00 [accepted]
PHST- 2020/02/18 06:00 [entrez]
PHST- 2020/02/18 06:00 [pubmed]
PHST- 2020/02/18 06:01 [medline]
PHST- 2020/02/10 00:00 [pmc-release]
AID - 238 [pii]
AID - 10.1186/s12950-020-0238-7 [doi]
PST - epublish
SO  - J Inflamm (Lond). 2020 Feb 10;17:5. doi: 10.1186/s12950-020-0238-7. eCollection 
      2020.