title: Dexamethasone Down-Regulates Expression of Triggering Receptor Expressed on Myeloid Cells-1: Evidence for a TNFα-Related Effect.
abstract: OBJECTIVE
  To investigate the effect of dexamethasone on triggering receptor expressed on myeloid cells-1 (TREM-1).
  
  
  METHODS
  Wild-type and tumor necrosis factor (TNF (-/-)) mice were pre-treated with saline, dexamethasone, or hydrocortisone and exposed to a lethal infection of Pseudomonas aeruginosa. Mortality and TREM-1 on neutrophil membranes was measured after sacrifice. U937 human monocytic cells were stimulated with lipopolysaccharide (LPS) or heat-killed P. aeruginosa without or with dexamethasone or hydrocortisone, and cell-surface TREM-1 and soluble TREM-1 (sTREM-1) were quantified. Expression of TREM-1 and sTREM-1 was also studied in LPS-stimulated U937 cells incubated in the absence or presence of TNFα or anti-TNFα antibody.
  
  
  RESULTS
  Pre-treatment with dexamethasone, but not hydrocortisone, prolonged animal survival. Mice pre-treated with dexamethasone showed decreased expression of TREM-1 on neutrophils. In U937 cells, LPS or heat-killed P. aeruginosa induced the expression of TREM-1 and the release of sTREM-1. U937 TREM-1 and sTREM-1 were decreased upon addition of dexamethasone but not hydrocortisone. The suppressive effect of dexamethasone was enhanced in the presence of exogenous TNFα and lost in the presence of anti-TNFα antibody. In TNF (-/-) mice, dexamethasone suppression of mortality and TREM-1 neutrophil expression was lost. Gene expression of TREM-1 in U937 monocytes was decreased after treatment with dexamethasone.
  
  
  CONCLUSIONS
  TREM-1/sTREM-1 is a novel site of action of dexamethasone. This action is associated with down-regulation of gene expression and is mediated by TNFα.
authors.affiliation: 4th Department of Internal Medicine, University of Athens Medical School , Athens , Greece.
authors.forename: Ira
authors.initials: I
authors.lastname: Mihailidou
authors.affiliation: 4th Department of Internal Medicine, University of Athens Medical School , Athens , Greece.
authors.forename: Aimilia
authors.initials: A
authors.lastname: Pelekanou
authors.affiliation: 4th Department of Internal Medicine, University of Athens Medical School , Athens , Greece.
authors.forename: Aikaterini
authors.initials: A
authors.lastname: Pistiki
authors.affiliation: 4th Department of Internal Medicine, University of Athens Medical School , Athens , Greece.
authors.forename: Aikaterini
authors.initials: A
authors.lastname: Spyridaki
authors.affiliation: 4th Department of Internal Medicine, University of Athens Medical School , Athens , Greece.
authors.forename: Ira-Maria
authors.initials: IM
authors.lastname: Tzepi
authors.affiliation: 4th Department of Internal Medicine, University of Athens Medical School , Athens , Greece.
authors.forename: Georgia
authors.initials: G
authors.lastname: Damoraki
authors.affiliation: 4th Department of Internal Medicine, University of Athens Medical School , Athens , Greece ; Integrated Research and Treatment Center, Center for Sepsis Control and Care, Jena University Hospital , Jena , Germany.
authors.forename: Evangelos J
authors.initials: EJ
authors.lastname: Giamarellos-Bourboulis
keywords: Pseudomonas aeruginosa; TNFα; TREM-1; dexamethasone; monocytes