PMID- 25210730
OWN - NLM
STAT- MEDLINE
DCOM- 20151026
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 9
IP  - 9
DP  - 2014
TI  - Salusin-beta, but not salusin-alpha, promotes human umbilical vein endothelial cell 
      inflammation via the p38 MAPK/JNK-NF-kappaB pathway.
PG  - e107555
LID - 10.1371/journal.pone.0107555 [doi]
LID - e107555
AB  - OBJECTIVE: Recently, salusin-beta has been reported to have pro-atherosclerotic 
      effects, but salusin-alpha has anti-atherosclerotic effects. Our previous study has 
      shown that salusin-beta but not salusin-alpha promotes vascular inflammation in 
      apoE-deficient mice. However, the underlying mechanism remains unknown. In this 
      study, we observed the effect of salusins on inflammatory responses and the 
      MAPK-NF-kappaB signaling pathway in human umbilical vein endothelial cells (HUVECs). 
      METHODS AND RESULTS: HUVECs were incubated with different concentrations of 
      salusin-alpha and salusin-beta. The levels of interleukin-6 (IL-6) and tumor necrosis 
      factor-alpha (TNF-alpha) were determined using enzyme-linked immunosorbent assay (ELISA). 
      The mRNA expressions of vascular cell adhesion molecule-1 (VCAM-1) and monocyte 
      chemoattractant protein-1 (MCP-1) were quantified using quantitative real-time 
      polymerase chain reaction (PCR). The protein expressions of VCAM-1, MCP-1, I-kappaBalpha, 
      NF-kappaB, p-JNK and p-p38 MAPK were measured using western blotting analysis. Our 
      results showed that in HUVECs, salusin-beta could up-regulate the levels of IL-6, 
      TNF-alpha, VCAM-1 and MCP-1, promote I-kappaBalpha degradation and NF-kappaB activation, and 
      increase the phosphorylation of JNK and p38 MAPK. These effects could be 
      inhibited by p38 MAPK inhibitor SB203580 and/or JNK inhibitor SP600125. In 
      contrast, salusin-alpha could selectively decrease VCAM-1 protein, but did not show 
      any effect on the expressions of VCAM-1 mRNA, TNF-alpha, IL-6, MCP-1, I-kappaBalpha, NF-kappaB, 
      p-JNK or p-p38 MAPK. CONCLUSION: Salusin-beta was able to promote inflammatory 
      responses in HUVECs via the p38 MAPK-NF-kappaB and JNK-NF-kappaB pathways. In contrast, 
      salusin-alpha failed to show any significant effects on the inflammatory responses in 
      HUVECs. These results provide further insight into the mechanisms behind salusins 
      in vascular inflammation and offer a potential target for the prevention and 
      treatment of atherosclerosis.
FAU - Zhou, Cheng-Hua
AU  - Zhou CH
AD  - School of Pharmacy, Xuzhou Medical College, Xuzhou, China.
FAU - Pan, Jin
AU  - Pan J
AD  - School of Pharmacy, Xuzhou Medical College, Xuzhou, China.
FAU - Huang, He
AU  - Huang H
AD  - Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, 
      Xuzhou, China.
FAU - Zhu, Yangzi
AU  - Zhu Y
AD  - Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, 
      Xuzhou, China.
FAU - Zhang, Mingxing
AU  - Zhang M
AD  - School of Pharmacy, Xuzhou Medical College, Xuzhou, China.
FAU - Liu, Lian
AU  - Liu L
AD  - School of Pharmacy, Xuzhou Medical College, Xuzhou, China.
FAU - Wu, Yuqing
AU  - Wu Y
AD  - Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, 
      Xuzhou, China; Department of Anesthetic Pharmacology, Xuzhou Medical College, 
      Xuzhou, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140911
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (IL6 protein, human)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Interleukin-6)
RN  - 0 (NF-kappa B)
RN  - 0 (TNF protein, human)
RN  - 0 (TOR2A protein, human)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Vascular Cell Adhesion Molecule-1)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Cells, Cultured
MH  - Chemokine CCL2/metabolism
MH  - Human Umbilical Vein Endothelial Cells/*immunology/metabolism
MH  - Humans
MH  - Inflammation Mediators/metabolism
MH  - Intercellular Signaling Peptides and Proteins/*physiology
MH  - Interleukin-6/metabolism
MH  - JNK Mitogen-Activated Protein Kinases/metabolism
MH  - *MAP Kinase Signaling System
MH  - NF-kappa B/metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - Vascular Cell Adhesion Molecule-1/metabolism
MH  - Vasculitis/metabolism
MH  - p38 Mitogen-Activated Protein Kinases/metabolism
PMC - PMC4161457
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2014/09/12 06:00
MHDA- 2015/10/27 06:00
PMCR- 2014/09/11
CRDT- 2014/09/12 06:00
PHST- 2014/04/29 00:00 [received]
PHST- 2014/08/14 00:00 [accepted]
PHST- 2014/09/12 06:00 [entrez]
PHST- 2014/09/12 06:00 [pubmed]
PHST- 2015/10/27 06:00 [medline]
PHST- 2014/09/11 00:00 [pmc-release]
AID - PONE-D-14-19243 [pii]
AID - 10.1371/journal.pone.0107555 [doi]
PST - epublish
SO  - PLoS One. 2014 Sep 11;9(9):e107555. doi: 10.1371/journal.pone.0107555. 
      eCollection 2014.