title: Propofol inhibits cyclo-oxygenase activity in human monocytic THP-1 cells.
abstract: OBJECTIVE
  Monocytes/macrophages are key players in innate and adaptive immunity. Upon stimulation, they secrete prostanoids, which are produced by cyclooxygenase from arachidonic acid. Prostanoids influence inflammation and immune responses. We investigated the effect of propofol on prostaglandin E(2) and thromboxane B(2) production by the human monocytic cell line THP-1.
  
  
  METHODS
  The THP-1 cells were cultured with lipopolysaccharide (1 microg ml(-1)) in the presence of clinically relevant sedative/anesthetic concentrations of propofol (0-30 microM) for 18 h, and the concentration of prostaglandin E(2) and thromboxane B(2) in culture supernatants was measured using an enzyme immunoassay. Intracellular cyclooxygenase protein expression was measured by flow cytometry. Cyclooxygenase activity was assessed by measuring production of prostaglandin E(2) and thromboxane B(2) by THP-1 cells after arachidonic acid (10 microM) substrate provision.
  
  
  RESULTS
  Propofol decreased the production of prostaglandin E(2) (75.4 +/- 6.4 pg ml(-1) at 0 microM vs. 28.5 +/- 11.2 pg ml(-1) at 30 microM; P < 0.001) and thromboxane B(2) (282.4 +/- 79.2 pg ml(-1) at 0 microM vs. 40.4 +/- 21.7 pg ml(-1) at 30 microM; P < 0.001). The inhibition was not due to the decreased cyclooxygenase protein expression because intracellular staining of this enzyme was not affected by propofol. After arachidonic acid provision, prostaglandin E(2) and thromboxane B(2) production from activated THP-1 cells was significantly (P < 0.001) decreased with propofol, indicating direct suppression of cyclooxygenase activity with propofol.
  
  
  CONCLUSIONS
  Propofol may modulate inflammation via the suppression of cyclooxygenase activity. Through the inhibition of prostanoid production, propofol may enhance immune responses.
authors.affiliation: Department of Anesthesiology, Kansai Medical University, 10-15, Fumizono-cho, Moriguchi, Osaka 570-8507, Japan. nvkc20988@hera.eonet.ne.jp
authors.forename: Takefumi
authors.initials: T
authors.lastname: Inada
authors.forename: Kozue
authors.initials: K
authors.lastname: Kubo
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kambara
authors.forename: Koh
authors.initials: K
authors.lastname: Shingu
mesh_terms: D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D051545:Cyclooxygenase 1 / Q000096:biosynthesis / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000096:biosynthesis / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors; D015232:Dinoprostone / Q000096:biosynthesis; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects / Q000201:enzymology; D015742:Propofol / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000096:biosynthesis
chemical_list: D018686:Anesthetics, Intravenous; D016861:Cyclooxygenase Inhibitors; D008070:Lipopolysaccharides; D013928:Thromboxane A2; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D015232:Dinoprostone; D015742:Propofol