AUTHOR=Mihailidou Ira , Pelekanou Aimilia , Pistiki Aikaterini , Spyridaki Aikaterini , Tzepi Ira-Maria , Damoraki Georgia , Giamarellos-Bourboulis Evangelos J.

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

JOURNAL=Frontiers in Public Health

VOLUME=1

YEAR=2013

URL=https://www.frontiersin.org/journals/public-health/articles/10.3389/fpubh.2013.00050

DOI=10.3389/fpubh.2013.00050

ISSN=2296-2565

ABSTRACT=<p><bold>Objectives:</bold> To investigate the effect of dexamethasone on triggering receptor expressed on myeloid cells-1 (TREM-1).</p><p><bold>Methods:</bold> Wild-type and tumor necrosis factor (<italic>TNF</italic><sup>−/−</sup>) mice were pre-treated with saline, dexamethasone, or hydrocortisone and exposed to a lethal infection of <italic>Pseudomonas aeruginosa</italic>. Mortality and TREM-1 on neutrophil membranes was measured after sacrifice. U937 human monocytic cells were stimulated with lipopolysaccharide (LPS) or heat-killed <italic>P. aeruginosa</italic> 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.</p><p><bold>Results:</bold> 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 <italic>P. aeruginosa</italic> 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 <italic>TNF</italic><sup>−/−</sup> mice, dexamethasone suppression of mortality and TREM-1 neutrophil expression was lost. Gene expression of <italic>TREM-1</italic> in U937 monocytes was decreased after treatment with dexamethasone.</p><p><bold>Conclusion:</bold> 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.</p>