title: Chitosan oligosaccharides suppress LPS-induced IL-8 expression in human umbilical vein endothelial cells through blockade of p38 and Akt protein kinases.
abstract: OBJECTIVE
  To investigate whether and how COS inhibited IL-8 production in LPS-induced human umbilical vein endothelial cells (HUVECs).
  
  
  METHODS
  RT-PCR, enzyme-linked immunosorbent assays (ELISA) and Western blotting were used to study IL-8 expression and related signaling pathway. Wound healing migration assays and monocytic cell adhesion analysis were used to explore the chemotactic and adhesive activities of HUVECs.
  
  
  RESULTS
  COS 50-200 μg/mL exerted a significant inhibitory effect on LPS 100 ng/mL-induced IL-8 expression in HUVECs at both the transcriptional and translational levels. In addition, COS 50-200 μg/mL inhibited LPS-induced HUVEC migration and U937 monocyte adhesion to HUVECs in a concentration-dependent manner. Signal transduction studies suggest that COS blocked LPS-induced activation of nuclear factor-κB (NF-κB) and activator protein-1 (AP-1) as well as phosphorylation of p38 mitogen-activated protein kinase (MAPK) and phosphokinase Akt. Further, the over-expression of LPS-induced IL-8 mRNA in HUVECs was suppressed by a p38 MAPK inhibitor (SB203580, 25 μmol/L) or a phosphatidylinositol 3-kinase (PI3K) inhibitor (LY294002, 50 μmol/L).
  
  
  CONCLUSIONS
  COS inhibited LPS-induced IL-8 expression in HUVECs through the blockade of the p38 MAPK and PI3K/Akt signaling pathways.
authors.affiliation: Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China.
authors.forename: Hong-tao
authors.initials: HT
authors.lastname: Liu
authors.forename: Pei
authors.initials: P
authors.lastname: Huang
authors.forename: Pan
authors.initials: P
authors.lastname: Ma
authors.forename: Qi-shun
authors.initials: QS
authors.lastname: Liu
authors.forename: Chao
authors.initials: C
authors.lastname: Yu
authors.forename: Yu-guang
authors.initials: YG
authors.lastname: Du
mesh_terms: D001483:Base Sequence; D002478:Cells, Cultured; D048271:Chitosan / Q000494:pharmacology*; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D016209:Interleukin-8 / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D009844:Oligosaccharides / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014471:Umbilical Veins / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D016209:Interleukin-8; D008070:Lipopolysaccharides; D009844:Oligosaccharides; D048271:Chitosan; D048051:p38 Mitogen-Activated Protein Kinases