title: Dexamethasone and RU24858 Induce Survival and Growth Factor Receptor Bound Protein 2, Leukotriene B4 Receptor 1 and Annexin-1 Expression in Primary Human Neutrophils.
abstract: Glucocorticoids are widely used anti-inflammatory medication in diseases like asthma and chronic obstructive pulmonary disease. Glucocorticoids can either activate (transactivation) or inhibit (transrepression) transcription. RU24858 was introduced as a "dissociated" glucocorticoid and it has been reported to transrepress but not to transactivate. The aim of this study was to compare the effects of RU24858 and dexamethasone in human neutrophils. RU24858 delayed spontaneous neutrophil apoptosis and further enhanced GM-CSF- induced neutrophil survival to a similar extent as dexamethasone. Like dexamethasone RU24858 also reduced CXCL8 and MIP-1α. Unexpectedly however, RU24858 increased the expression of the glucocorticoid-inducible genes BLT-1, Annexin-1 and Grb-2 in neutrophils to a similar level as seen with dexamethasone. We have shown here that dexamethasone and RU24858 both increase Grb-2, BLT1 and Annexin-1 expression and inhibit CXCL8 and MIP-1α production. This suggests that RU24858 was not able to dissociate between transactivation and transrepression in human neutrophils but enhanced neutrophil survival.
authors.affiliation: The Immunopharmacology Research Group, University of Tampere School of Medicine and Tampere University Hospital Tampere Finland.
authors.forename: Mirkka
authors.initials: M
authors.lastname: Janka-Junttila
authors.affiliation: The Immunopharmacology Research Group, University of Tampere School of Medicine and Tampere University Hospital Tampere Finland.
authors.forename: Hannele
authors.initials: H
authors.lastname: Hasala
authors.affiliation: Airways Disease, National Heart and Lung Institute, Imperial College, London, UK.
authors.forename: Ian
authors.initials: I
authors.lastname: Adcock
authors.affiliation: The Immunopharmacology Research Group, University of Tampere School of Medicine and Tampere University Hospital Tampere Finland.
authors.forename: Eeva
authors.initials: E
authors.lastname: Moilanen
authors.affiliation: The Immunopharmacology Research Group, University of Tampere School of Medicine and Tampere University Hospital Tampere Finland. ; Department of Respiratory Medicine, Seinäjoki Central Hospital, Seinäjoki, Finland.
authors.forename: Hannu
authors.initials: H
authors.lastname: Kankaanranta
keywords: apoptosis; dexamethasone; glucocorticoids; neutrophils; transactivation; transrepression