title: Indobufen inhibits tissue factor in human monocytes through a thromboxane-mediated mechanism.
abstract: OBJECTIVE
  To assess whether indobufen, a reversible inhibitor of platelet cyclooxygenase (Cox) activity, affects tissue factor (TF) in human monocytes and to investigate the relationship between Cox-derived products and TF.
  
  
  METHODS
  TF was evaluated in isolated adherent monocytes, both resting and lipopolysaccharide (LPS)-stimulated, in terms of procoagulant activity, protein, and mRNA levels. The expression of TF surface antigen was determined in LPS-stimulated whole blood monocytes by flow cytometry. The levels of the stable thromboxane A2 (TxA2) metabolite, TxB2, and of prostaglandin E2 (PGE2) were measured in monocyte supernatant by immunoenzymatic techniques. Cox-1 and Cox-2 protein level, tyrosine phosphorylation, and mitogen-activated protein kinase (MAP-kinase) activation were determined by Western blot analysis.
  
  
  RESULTS
  Indobufen prevents TF expression and activity both in isolated and in whole blood monocytes. Reduction of TxA2 synthesis, coupled with a lack of effect on PGE2 levels and prevention of ERK1/2 phosphorylation are highlighted as the mechanisms through which indobufen negatively affects TF.
  
  
  CONCLUSIONS
  Data show that indobufen down-regulates TF in monocytes. This novel activity, coupled with the antiplatelet effect of the drug, may add benefit for its use in the management of atherothrombosis.
authors.affiliation: E. Grossi Paoletti Center, Department of Pharmacological Sciences, Via Balzaretti 9, 20133 Milan, Italy.
authors.forename: Sonia
authors.initials: S
authors.lastname: Eligini
authors.forename: Francesco
authors.initials: F
authors.lastname: Violi
authors.forename: Cristina
authors.initials: C
authors.lastname: Banfi
authors.forename: Silvia S
authors.initials: SS
authors.lastname: Barbieri
authors.forename: Marta
authors.initials: M
authors.lastname: Brambilla
authors.forename: Mirella
authors.initials: M
authors.lastname: Saliola
authors.forename: Elena
authors.initials: E
authors.lastname: Tremoli
authors.forename: Susanna
authors.initials: S
authors.lastname: Colli
mesh_terms: D002478:Cells, Cultured; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D003864:Depression, Chemical; D015232:Dinoprostone / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D054833:Isoindoles; D008070:Lipopolysaccharides; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D010654:Phenylbutyrates / Q000494:pharmacology*; D013925:Thromboplastin / Q000032:analysis* / Q000378:metabolism; D013928:Thromboxane A2 / Q000032:analysis; D013929:Thromboxane B2 / Q000032:analysis; D013931:Thromboxanes / Q000378:metabolism*
chemical_list: D016861:Cyclooxygenase Inhibitors; D054833:Isoindoles; D008070:Lipopolysaccharides; D010654:Phenylbutyrates; D013931:Thromboxanes; D013929:Thromboxane B2; D013928:Thromboxane A2; C020371:indobufen; D013925:Thromboplastin; D015232:Dinoprostone