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Dexamethasone enhances LPS induction of tissue factor expression in human monocytic cells by increasing tissue factor mRNA stability
Author(s) -
Reddy K. Veera,
Bhattacharjee Gourab,
Schabbauer Gernot,
Hollis Angela,
Kempf Kevin,
Tencati Michael,
O’Connell Maria,
Guha Mausumee,
Mackman Nigel
Publication year - 2004
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0204068
Subject(s) - tissue factor , monocyte , biology , messenger rna , tumor necrosis factor alpha , microbiology and biotechnology , lipopolysaccharide , gene expression , transcription factor , endocrinology , medicine , immunology , gene , coagulation , biochemistry
Glucocorticoids, such as dexamethasone (Dex), are used clinically in the treatment of various inflammatory diseases. Dex acts by inhibiting the expression of inflammatory mediators, such as tumor necrosis factor α (TNF‐α) and monocyte chemoattractant protein‐1 (MCP‐1). It is surprising that Dex enhances bacterial lipopolysaccharide (LPS) induction of tissue factor (TF) expression in human monocytic cells. TF is a transmembrane glycoprotein that activates the coagulation 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 transcription but increased the stability of TF mRNA. Dex decreased the stability of MCP‐1 mRNA and did not affect TNF‐α mRNA stability. Finally, we showed that Dex increased the stability of a transcript consisting of the final 297 nucleotides of the TF mRNA in in vitro decay assays. This region contains AU‐rich elements that regulate mRNA stability and may mediate the Dex response. Therefore, despite an inhibition of TF gene transcription, Dex enhances TF expression in human monocytic cells by increasing the stability of TF mRNA.