Dexamethasone enhances LPS induction of tissue factor expression in human monocytic cells by increasing tissue factor mRNA stability

Glucocorticoids, such as dexametha- sone (Dex), are used clinically in the treatment of various inflammatory diseases. Dex acts by inhib- iting the expression of inflammatory mediators, such as tumor necrosis factor (TNF-) and monocyte chemoattractant protein-1 (MCP-1). It is surprising that Dex enhances bacterial lipopoly- saccharide (LPS) induction of tissue factor (TF) expression in human monocytic cells. TF is a trans- membrane glycoprotein that activates the coagula- tion protease cascade. In this study, we analyze the mechanism by which Dex enhances LPS-induced TF expression in human monocytic cells. We found that Dex reduced LPS-induced TF gene transcrip- tion but increased the stability of TF mRNA. Dex decreased the stability of MCP-1 mRNA and did not affect TNF- mRNA stability. Finally, we showed that Dex increased the stability of a tran- script consisting of the final 297 nucleotides of the TF mRNA in in vitro decay assays. This region contains AU-rich elements that regulate mRNA sta- bility and may mediate the Dex response. There- fore, despite an inhibition of TF gene transcrip- tion, Dex enhances TF expression in human mono- cytic cells by increasing the stability of TF mRNA. J. Leukoc. Biol. 76: 145-151; 2004.