title: Histamine differentially interacts with tumor necrosis factor-alpha and thrombin in endothelial tissue factor induction: the role of c-Jun NH2-terminal kinase.
abstract: BACKGROUND
  Histamine plays an important role in vascular disease. Tissue factor (TF) expression is induced in vascular inflammation and acute coronary syndromes.
  
  
  OBJECTIVE
  This study examined the effect of histamine on tumor necrosis factor-alpha- (TNF-alpha-) vs. thrombin-induced endothelial TF expression.
  
  
  RESULTS
  Histamine (10(-8)-10(-5) mol L-1), TNF-alpha (5 ng mL-1), and thrombin (1 U mL-1) induced TF expression in human endothelial cells. Although TF expression by TNF-alpha and thrombin was identical, histamine augmented TNF-alpha-induced expression 7.0-fold, but thrombin-induced expression only 2.6-fold. Similar responses occurred with TF activity. The H1-receptor antagonist mepyramine abrogated these effects. Differential augmentation by histamine was also observed at the mRNA level. Histamine-induced p38 activation preceded a weak second activation to both TNF-alpha and thrombin. Histamine-induced c-Jun NH2-terminal kinase (JNK) activation was followed by a strong second activation to TNF-alpha, and less to thrombin. Selective inhibition of this second JNK activation by SP600125 reduced TF induction to histamine plus TNF-alpha by 67%, but to histamine plus thrombin by only 32%. Histamine augmented TNF-alpha- and thrombin-induced vascular cell adhesion molecule 1 (VCAM-1) expression to a similar extent. Consistent with this observation, VCAM-1 induction to TNF-alpha and thrombin was mediated by p38, but not by JNK.
  
  
  CONCLUSIONS
  Histamine differentially augments TNF-alpha- vs. thrombin-induced TF expression and activity, which is mediated by the H1-receptor, occurs at the mRNA level, and is related to differential JNK activation.
authors.affiliation: Cardiovascular Research, Physiology Institute, University of Zürich, and Cardiology, Cardiovascular Center, University Hospital Zürich, Switzerland.
authors.forename: J
authors.initials: J
authors.lastname: Steffel
authors.forename: C
authors.initials: C
authors.lastname: Arnet
authors.forename: A
authors.initials: A
authors.lastname: Akhmedov
authors.forename: S M
authors.initials: SM
authors.lastname: Iseli
authors.forename: T F
authors.initials: TF
authors.lastname: Lüscher
authors.forename: F C
authors.initials: FC
authors.lastname: Tanner
mesh_terms: D000208:Acute Disease; D000873:Anthracenes / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects; D002478:Cells, Cultured; D003327:Coronary Disease / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D004789:Enzyme Activation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006490:Hemostatics / Q000494:pharmacology*; D006632:Histamine / Q000494:pharmacology*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011969:Receptors, Histamine H1 / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013577:Syndrome; D013917:Thrombin / Q000494:pharmacology*; D013925:Thromboplastin / Q000096:biosynthesis*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis; D014657:Vasculitis / Q000378:metabolism*
chemical_list: D000873:Anthracenes; D006490:Hemostatics; D011969:Receptors, Histamine H1; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; C432165:pyrazolanthrone; D006632:Histamine; D013925:Thromboplastin; D048031:JNK Mitogen-Activated Protein Kinases; D013917:Thrombin