BACKGROUND: Glucocorticoids have been shown to inhibit human neutrophil apoptosis, with implications that this might help accentuate neutrophilic inflammation. OBJECTIVE: The aim of this study was to investigate the molecular mechanisms involved in glucocorticoid-mediated inhibition of primary human neutrophil apoptosis. METHODS: Primary human neutrophils were isolated from peripheral blood of healthy volunteers and cultured in vitro with dexamethasone. RESULTS: Here we confirm that dexamethasone, a classical glucocorticoid, significantly inhibited apoptosis of primary human neutrophils. This inhibition was not dependent on transrepression of proapoptotic molecules but was associated with induction of antiapoptotic Mcl-1. Remarkably, glucocorticoid-mediated enhancement of Mcl-1 and survival were significantly suppressed by pharmacologic inhibition of p38 mitogen-activated protein kinase or phosphatidylinositol 3-kinase. Inhibition of the above kinases also blocked glucocorticoid-induced maintenance of mitochondrial transmembrane potential and suppression of caspases. CONCLUSION: Phosphatidylinositol 3-kinase and p38 mitogen-activated protein kinase are protein kinases that regulate the prosurvival effect of glucocorticoids on human neutrophils.
BACKGROUND: Glucocorticoids have been shown to inhibit human neutrophil apoptosis, with implications that this might help accentuate neutrophilic inflammation. OBJECTIVE: The aim of this study was to investigate the molecular mechanisms involved in glucocorticoid-mediated inhibition of primary human neutrophil apoptosis. METHODS: Primary human neutrophils were isolated from peripheral blood of healthy volunteers and cultured in vitro with dexamethasone. RESULTS: Here we confirm that dexamethasone, a classical glucocorticoid, significantly inhibited apoptosis of primary human neutrophils. This inhibition was not dependent on transrepression of proapoptotic molecules but was associated with induction of antiapoptotic Mcl-1. Remarkably, glucocorticoid-mediated enhancement of Mcl-1 and survival were significantly suppressed by pharmacologic inhibition of p38 mitogen-activated protein kinase or phosphatidylinositol 3-kinase. Inhibition of the above kinases also blocked glucocorticoid-induced maintenance of mitochondrial transmembrane potential and suppression of caspases. CONCLUSION: Phosphatidylinositol 3-kinase and p38 mitogen-activated protein kinase are protein kinases that regulate the prosurvival effect of glucocorticoids on human neutrophils.
Authors: F M C Silva; E E Oliveira; A C C Gouveia; A S S Brugiolo; C C Alves; J O A Correa; J Gameiro; J Mattes; H C Teixeira; A P Ferreira Journal: Clin Exp Immunol Date: 2017-03-31 Impact factor: 4.330
Authors: Muhammad Wasim; Michela Carlet; Muhammad Mansha; Richard Greil; Christian Ploner; Alexander Trockenbacher; Johannes Rainer; Reinhard Kofler Journal: J Steroid Biochem Mol Biol Date: 2010-05-06 Impact factor: 4.292