Dexamethasone Down-Regulates Expression of Triggering Receptor Expressed on Myeloid Cells-1: Evidence for a TNFα-Related Effect

• Published in: Frontiers in public health 2013, Vol.1, p.50-50
• Main Authors: Mihailidou, Ira, Pelekanou, Aimilia, Pistiki, Aikaterini, Spyridaki, Aikaterini, Tzepi, Ira-Maria, Damoraki, Georgia, Giamarellos-Bourboulis, Evangelos J
• Format: Article
• Language: English
• Subjects: Public Health
• ISSN: 2296-2565; 2296-2565
• DOI: 10.3389/fpubh.2013.00050

To investigate the effect of dexamethasone on triggering receptor expressed on myeloid cells-1 (TREM-1). 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. 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. 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.