title: Salusin-β, but not salusin-α, promotes human umbilical vein endothelial cell inflammation via the p38 MAPK/JNK-NF-κB pathway.
abstract: OBJECTIVE
  Recently, salusin-β has been reported to have pro-atherosclerotic effects, but salusin-α has anti-atherosclerotic effects. Our previous study has shown that salusin-β but not salusin-α 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-κB signaling pathway in human umbilical vein endothelial cells (HUVECs).
  
  
  RESULTS
  HUVECs were incubated with different concentrations of salusin-α and salusin-β. The levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) 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-κBα, NF-κB, p-JNK and p-p38 MAPK were measured using western blotting analysis. Our results showed that in HUVECs, salusin-β could up-regulate the levels of IL-6, TNF-α, VCAM-1 and MCP-1, promote I-κBα degradation and NF-κB 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-α could selectively decrease VCAM-1 protein, but did not show any effect on the expressions of VCAM-1 mRNA, TNF-α, IL-6, MCP-1, I-κBα, NF-κB, p-JNK or p-p38 MAPK.
  
  
  CONCLUSIONS
  Salusin-β was able to promote inflammatory responses in HUVECs via the p38 MAPK-NF-κB and JNK-NF-κB pathways. In contrast, salusin-α 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.
authors.affiliation: School of Pharmacy, Xuzhou Medical College, Xuzhou, China.
authors.forename: Cheng-Hua
authors.initials: CH
authors.lastname: Zhou
authors.affiliation: School of Pharmacy, Xuzhou Medical College, Xuzhou, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Pan
authors.affiliation: Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou, China.
authors.forename: He
authors.initials: H
authors.lastname: Huang
authors.affiliation: Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou, China.
authors.forename: Yangzi
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: School of Pharmacy, Xuzhou Medical College, Xuzhou, China.
authors.forename: Mingxing
authors.initials: M
authors.lastname: Zhang
authors.affiliation: School of Pharmacy, Xuzhou Medical College, Xuzhou, China.
authors.forename: Lian
authors.initials: L
authors.lastname: Liu
authors.affiliation: Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou, China; Department of Anesthetic Pharmacology, Xuzhou Medical College, Xuzhou, China.
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Wu
mesh_terms: D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology*; D015850:Interleukin-6 / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D020935:MAP Kinase Signaling System; D016328:NF-kappa B / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D014657:Vasculitis / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; C508600:IL6 protein, human; D018836:Inflammation Mediators; D036341:Intercellular Signaling Peptides and Proteins; D015850:Interleukin-6; D016328:NF-kappa B; C439524:TNF protein, human; C478739:TOR2A protein, human; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases