title: Concentration dependent anti-inflammatory effects thrombin on polyphosphate-mediated inflammatory responses in vitro and in vivo.
abstract: OBJECTIVE
  Recent results indicate that polyphosphate (polyP) released by human endothelial cells can function as a pro-inflammatory mediator, and it has been reported that low thrombin concentrations mediate anti-inflammatory activities. This study was undertaken to investigate whether low thrombin concentrations can modulate polyP-mediated inflammatory responses in human umbilical vein endothelial cells (HUVECs) and in mice.
  
  
  METHODS
  Concentration dependent anti-inflammatory effects of thrombin such as barrier protection, inhibition of cell adhesion molecule expression and inhibition of monocytes adhesion and migration toward human endothelial cells against polyP-mediated pro-inflammatory activities were tested in vitro and in vivo. The concentration-dependent effects of thrombin on polyP-induced nuclear factor (NF)-κB activation and the production of tumor necrosis factor (TNF)-α and interleukin (IL)-6 were also tested.
  
  
  RESULTS
  We found that at low concentrations (25-75 pM), thrombin inhibits polyP-mediated barrier disruption, the expressions of cell adhesion molecules, and leukocyte to HUVEC adhesion/migration. Interestingly, polyP-induced NF-κB activation and the production of TNF-α and IL-6 were inhibited by low thrombin concentrations in HUVECs. These anti-inflammatory functions of thrombin were confirmed in polyP-injected mice.
  
  
  CONCLUSIONS
  These results suggest that thrombin at 25-75 pM may have therapeutic potential for various systemic inflammatory diseases.
authors.affiliation: Department of Anatomy and Histology, College of Oriental Medicine, Daegu Haany University, Gyeongsan 712-715, Republic of Korea.
authors.forename: Sae-Kwang
authors.initials: SK
authors.lastname: Ku
authors.forename: Jong-Sup
authors.initials: JS
authors.lastname: Bae
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000276:immunology; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D007962:Leukocytes / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010539:Permeability / Q000187:drug effects; D011122:Polyphosphates; D044463:Receptor, PAR-1 / Q000276:immunology; D013917:Thrombin / Q000008:administration & dosage*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; D015815:Cell Adhesion Molecules; D015850:Interleukin-6; D011122:Polyphosphates; D044463:Receptor, PAR-1; D014409:Tumor Necrosis Factor-alpha; D013917:Thrombin