PMID- 28420166
OWN - NLM
STAT- MEDLINE
DCOM- 20170629
LR  - 20211204
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 18
IP  - 4
DP  - 2017 Apr 17
TI  - Hypaphorine Attenuates Lipopolysaccharide-Induced Endothelial Inflammation via 
      Regulation of TLR4 and PPAR-gamma Dependent on PI3K/Akt/mTOR Signal Pathway.
LID - 10.3390/ijms18040844 [doi]
LID - 844
AB  - Endothelial lesion response to injurious stimuli is a necessary step for 
      initiating inflammatory cascades in blood vessels. Hypaphorine (Hy) from 
      different marine sources is shown to exhibit anti-inflammatory properties. 
      However, the potential roles and possible molecular mechanisms of Hy in 
      endothelial inflammation have yet to be fully clarified. We showed that Hy 
      significantly inhibited the positive effects of lipopolysaccharide (LPS) on 
      pro-inflammatory cytokines expressions, including tumor necrosis factor-alpha 
      (TNF-alpha), interleukin-1beta (IL-1beta), monocyte chemoattractant protein 1 (MCP-1) and 
      vascular cellular adhesion molecule-1 (VCAM-1), as well as induction of the 
      phosphorylation of Akt and mTOR in HMEC-1 cells. The downregulated peroxisome 
      proliferator-activated receptor gamma (PPAR-gamma) and upregulated toll-like receptor 4 
      (TLR4) expressions in LPS-challenged endothelial cells were prevented by Hy. 
      Inhibition of both PI3K and mTOR reversed LPS-stimulated increases in TLR4 
      expressions and decreases in PPAR-gamma levels. Genetic silencing of TLR4 or PPAR-gamma 
      agonist pioglitazone obviously abrogated the levels of pro-inflammatory cytokines 
      in LPS-treated HMEC-1 cells. These results suggest that Hy may exert 
      anti-inflammatory actions through the regulation of TLR4 and PPAR-gamma dependent on 
      PI3K/Akt/mTOR signal pathways. Hy may be considered as a therapeutic agent that 
      can potentially relieve or ameliorate endothelial inflammation-associated 
      diseases.
FAU - Sun, Haijian
AU  - Sun H
AD  - Department of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi 
      214122, China. haijsunjiangnan@jiangnan.edu.cn.
FAU - Zhu, Xuexue
AU  - Zhu X
AD  - Department of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi 
      214122, China. baojiangexz@sina.com.
FAU - Cai, Weiwei
AU  - Cai W
AD  - Department of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi 
      214122, China. hlxuzhou11@sina.com.
FAU - Qiu, Liying
AU  - Qiu L
AD  - Department of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi 
      214122, China. qiulydoc@163.com.
LA  - eng
PT  - Journal Article
DEP - 20170417
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Biomarkers)
RN  - 0 (Cytokines)
RN  - 0 (Indoles)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (PPAR gamma)
RN  - 0 (Toll-Like Receptor 4)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - GJ3358U63L (lenticin)
SB  - IM
MH  - Biomarkers
MH  - Cytokines/genetics/metabolism
MH  - Endothelium, Vascular/*drug effects/*metabolism/pathology
MH  - Enzyme Activation
MH  - Humans
MH  - Indoles/*pharmacology
MH  - Inflammation/*etiology/*metabolism/pathology
MH  - Inflammation Mediators/metabolism
MH  - Lipopolysaccharides/adverse effects
MH  - PPAR gamma/*metabolism
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Protein Binding
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - Signal Transduction/drug effects
MH  - TOR Serine-Threonine Kinases/*metabolism
MH  - Toll-Like Receptor 4/*metabolism
PMC - PMC5412428
OTO - NOTNLM
OT  - LPS
OT  - PPAR-gamma
OT  - TLR4
OT  - endothelial cells
OT  - inflammation
COIS- The authors declare no conflict of interest.
EDAT- 2017/04/20 06:00
MHDA- 2017/07/01 06:00
PMCR- 2017/04/01
CRDT- 2017/04/20 06:00
PHST- 2017/02/27 00:00 [received]
PHST- 2017/04/11 00:00 [revised]
PHST- 2017/04/13 00:00 [accepted]
PHST- 2017/04/20 06:00 [entrez]
PHST- 2017/04/20 06:00 [pubmed]
PHST- 2017/07/01 06:00 [medline]
PHST- 2017/04/01 00:00 [pmc-release]
AID - ijms18040844 [pii]
AID - ijms-18-00844 [pii]
AID - 10.3390/ijms18040844 [doi]
PST - epublish
SO  - Int J Mol Sci. 2017 Apr 17;18(4):844. doi: 10.3390/ijms18040844.