Objectives: 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 andTREM-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 solubleTREM-1 (sTREM-1) were quantified. Expression ofTREM-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 ofTREM-1 on neutrophils. In U937 cells, LPS or heat-killed P. aeruginosa induced the expression ofTREM-1 and the release of sTREM-1. U937TREM-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 ofTREM-1 in U937 monocytes was decreased after treatment with dexamethasone. Conclusion: 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 byTNFα.
CITATION STYLE
Mihailidou, I., Pelekanou, A., Pistiki, A., Spyridaki, A., Tzepi, I. M., Damoraki, G., & Giamarellos-Bourboulis, E. J. (2013). Dexamethasone down-regulates expression of triggering receptor expressed on myeloid cells-1: Evidence for a TNFα-related effect. Frontiers in Public Health, 1(NOV). https://doi.org/10.3389/fpubh.2013.00050
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