Department of Medicine , Jewish Hospital , Washington University Medical Center , St. Louis , Missouri 63110 .
J Biol Chem 266 : 13261-6 ( 1991)
Abstract
Macrophages and monocytes have essential roles in normal wound healing , in the immune response , and in the pathogenesis of atherosclerosis .
Platelet-derived growth factor ( PDGF ) stimulates the transcription of the early response gene , JE , and its human homolog , macrophage chemotactic protein-1 ( MCP-1 ) in fibroblasts .
JE/MCP-1 encodes a cytokine which is a member of a superfamily of small inducible genes that include platelet factor 4 , beta-thromboglobulin , 310-C/NAP-1/IL-8 , IP-10 , KC/gro/MGSA , and others which may play important roles in the inflammatory and immune response .
We now report that glucocorticoids inhibit the transcriptional induction of the JE gene by PDGF and serum in a dose-dependent manner .
The glucocorticoid response followed the expected anti-inflammatory rank order of potency and was not due to a shift in the time course of induction .
Nonsteroidal anti-inflammatory agents were ineffective in reducing JE mRNA levels .
Dexamethasone inhibited the accumulation of JE transcripts induced by PDGF , -O-tetradecanoylphorbol-13-acetate , and double-stranded synthetic RNA .
Nuclear runoff assays demonstrated that the negative regulation occurred by decreasing the transcriptional induction of the JE gene .
No effects on JE message stability could be detected in the presence of dexamethasone .
The protein synthesis inhibitors cycloheximide and puromycin reversed the glucocorticoid-mediated inhibition and suggested that new protein synthesis was necessary .
These results suggest that the transcriptional inhibition of glucocorticoids is mediated by the expression of a labile transcriptional repressor for the JE gene .
Gene Symbols
Chemical Identifiers ( Names)
Department of Obstetrics and Gynecology , Niigata University School of Medicine .
Nippon Sanka Fujinka Gakkai Zasshi 43 : 627-32 ( 1991)
Abstract
Trophoblasts taken from placental tissue of the 1st trimester and molar tissue , and GCH-1 ( gestational choriocarcinoma cell line ) cells were cultured in collagen coated dishes .
The medium used was a mixture of DME and Ham 's F-12 ( 1:1 ) , containing EGF , PDGF , insulin , GM-CSF , IL-1 , -2 , -3 , PGE1 and PGE2 in various concentrations .
3H-TdR uptake of the cultured cells was measured as a marker of cell growth .
The growth of normal trophoblasts was enhanced by PDGF or insulin , and remarkably by EGF + PDGF + insulin + GM-CSF .
The growth of molar trophoblasts was accelerated by EGF or insulin .
Under these culture conditions , normal trophoblasts have been successfully cultured and maintained for 12 months and molar trophoblasts for 9 months to date .
The cultured cells were identified with trophoblasts by immunohistochemical staining with CAM 5.2 monoclonal antibody .
No effect of growth factors was observed in GCH-1 cells .