Inhibition of tristetraprolin expression by dexamethasone in activated macrophages.
Tristetraprolin (TTP) is a factor that regulates mRNA stability and the expression of certain inflammatory genes. In the present study, we found that TTP expression was increased in macrophages exposed to bacterial lipopolysaccharide (LPS). Dexamethasone and dissociated steroid RU24858 inhibited LPS-induced TTP protein and mRNA expression and the inhibitory effect was reversed by a glucocorticoid receptor antagonist mifepristone. Histone deacetylase inhibitors trichostatin A (TSA) and apicidin reduced the inhibitory effect of dexamethasone and RU24858 on TTP expression, but the glucocorticoids did not alter TTP mRNA half-life. These results suggest that anti-inflammatory steroids reduce TTP expression in activated macrophages by a glucocorticoid response element (GRE)-independent mechanism, possibly through histone deacetylation and transcriptional silencing.
Jalonen
Ulla
U
The Immunopharmacological Research Group, University of Tampere, Medical School, FIN-33014 University of Tampere, Finland.
Lahti
Aleksi
A
Korhonen
Riku
R
Kankaanranta
Hannu
H
Moilanen
Eeva
E
D000818:Animals; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics*; D003899:Desoximetasone / Q000031:analogs & derivatives; D003907:Dexamethasone / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006655:Histone Deacetylases / Q000502:physiology; D006889:Hydroxycorticosteroids / Q000494:pharmacology; D017874:Immediate-Early Proteins / Q000235:genetics*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D012333:RNA, Messenger / Q000032:analysis; D051816:Tristetraprolin
D004268:DNA-Binding Proteins; D006889:Hydroxycorticosteroids; D017874:Immediate-Early Proteins; D008070:Lipopolysaccharides; D012333:RNA, Messenger; C000589029:RU24858; D051816:Tristetraprolin; C497553:Zfp36 protein, mouse; D003899:Desoximetasone; D003907:Dexamethasone; D006655:Histone Deacetylases