title: Differentiation and glucocorticoid regulated apopto-phagocytic gene expression patterns in human macrophages. Role of Mertk in enhanced phagocytosis.
abstract: The daily clearance of physiologically dying cells is performed safely mainly by cells in the mononuclear phagocyte system. They can recognize and engulf dying cells utilizing several cooperative mechanisms. In our study we show that the expression of a broad range of apopto-phagocytic genes is strongly up-regulated during differentiation of human monocytes to macrophages with different donor variability. The glucocorticoid dexamethasone has a profound effect on this process by selectively up-regulating six genes and down-regulating several others. The key role of the up-regulated mer tyrosine kinase (Mertk) in dexamethasone induced enhancement of phagocytosis could be demonstrated in human monocyte derived macrophages by gene silencing as well as blocking antibodies, and also in a monocyte-macrophage like cell line. However, the additional role of other glucocorticoid induced elements must be also considered since the presence of autologous serum during phagocytosis could almost completely compensate for the blocked function of Mertk.
authors: Apoptosis and Genomics Research Group, Department of Biochemistry and Molecular Biology, Hungarian Academy of Sciences, University of Debrecen, Debrecen, Hungary.
authors: Gábor
authors: G
authors: Zahuczky
authors: Endre
authors: E
authors: Kristóf
authors: Gyöngyike
authors: G
authors: Majai
authors: László
authors: L
authors: Fésüs
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000235:genetics*; D002454:Cell Differentiation / Q000187:drug effects*; D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D055785:Gene Knockdown Techniques; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D010587:Phagocytosis / Q000187:drug effects / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism*; D014019:Tissue Donors; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics; D000076202:c-Mer Tyrosine Kinase
chemical_list: D005938:Glucocorticoids; D011518:Proto-Oncogene Proteins; D003907:Dexamethasone; C097072:MERTK protein, human; D020794:Receptor Protein-Tyrosine Kinases; D000076202:c-Mer Tyrosine Kinase