The potentiating effect of glucocorticoids on the phagocytosis of apoptotic neutrophils, which can be inhibited by GCR antagonists, has been described. As an explanation of the enhanced phagocytic uptake of apoptotic cells, an increased capacity for engulfment oriented reorganization of cytoskeletal elements, loss of phosphorylation of adhesion mediators and increased eFT508 amount of Rac GTPase were considered. By analyzing the GC-induced expression patterns in human monocytes by microarray technology the following pathways and gene-clusters were proposed as possible functional markers of the developing anti-inflammatory subtype: up-regulated antioxidative, migration/chemotaxis, phagocytosis, anti-inflammatory genes and down-regulated T-cell chemotaxis, adhesion, apoptosis, oxidative functions and IFNc regulated genes.. The importance of Mer tyrosine kinase, as a member of of the Tyro3/Axl/Mer family of receptor tyrosine kinases in the engulfment and efficient clearance of apoptotic cells has been clearly demonstrated and it was recently found that the glucocorticoid RAF709 inhibitor dexamethasone treated human monocyte derived macrophages exhibit augmented capacity of phagocytosis only in the presence of a serum factor that was identified as protein S, a ligand for Mertk.. Here, we investigated the effects of differentiation and treatment by DXM on the gene-expression pattern of HMDMs using a custom designed apopto-phagocyte panel. Our data show that during differentiation of monocytes to macrophages most of the apopto-phagocytic genes are highly up-regulated. Dexamethasone led to further up-regulation of 6 genes while some others were significantly down-regulated. Of the up-regulated ones only silencing of Mertk could prevent DXM-mediated increase in phagocytosis of apoptotic cells in a serum-independent manner; this observation was confirmed by applying blocking antibodies against Mertk and showing that in monocytic cell lines low level and lack of Mertk inducibility by DXM is accompanied by their inability to engulf apoptotic cells. To gain further information about the correlation between DXM mediated gene induction in macrophages and their phagocytosis capacity toward apoptotic neutrophils, the effect of DXM treatment on human macrophage like cell lines was also investigated.
Progesterone most likely have a compensatory effect on ductal outgrowth
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