Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.48 (transcriptase)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The gene encoding the receptor for macrophage colony-stimulating factor 1 (CSF-1), the c-fms protooncogene, is selectively expressed in immature and mature mononuclear phagocytes and trophoblasts. Exon 1 is expressed only in trophoblasts. Isolation and sequencing of genomic DNA flanking exon 2 of the murine c-fms gene revealed a TATA-less promoter with significant homology to human c-fms. Reverse transcriptase primer extension analysis using exon 2 primers identified multiple clustered transcription initiation sites. Their position was confirmed by RNase protection. The same primer extension products were detected in equal abundance from macrophage or nonmacrophage sources of RNA. c-fms mRNA is acutely down-regulated in primary macrophages by CSF-1, bacterial lipopolysaccharide (LPS), and phorbol myristate acetate (PMA). Each of these agents reduced the abundance of c-fms RNA detectable by primer extension using an exon 3 primer without altering the abundance of presumptive short c-fms transcripts detected with exon 2 primers. Primer extension analysis with an intron 2 primer detected products at greater abundance in nonmacrophages. Templates detected with the intronic primer were induced in macrophages by LPS, PMA, and CSF-1, suggesting that each of the agents caused a shift from full-length c-fms mRNA production to production of unspliced, truncated transcripts. The c-fms promoter functioned constitutively in the RAW264 macrophage cell line, the B-cell line MOPC.31C, and several nonhematopoietic cell lines. Macrophage-specific expression and responsiveness to selective repression by LPS and PMA was achieved by the incorporation of intron 2 into the c-fms promoter-reporter construct. The results suggest that expression of the c-fms gene in macrophages is controlled by sequences in intron 2 that act by regulating transcription elongation.
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PMID:Expression of mRNA encoding the macrophage colony-stimulating factor receptor (c-fms) is controlled by a constitutive promoter and tissue-specific transcription elongation. 849 48

Many previous studies in both mouse and human placenta have implicated a role for colony stimulating factor-1 (CSF-1) in the regulation of placental development. In this study we have examined CSF-1 production by an immortalized cell line (TCL-1) derived from the choriodecidua, transfected with a retrovirus gene coding for the large-T antigen. TCL-1 cells were uniformly positive by immunocytochemistry for the composite sub-units of human chorionic g gonadotrophin (hCG) but were negative for markers of other cell types localized at the fetal-maternal interface. Gelatinase enzymes were secreted by TCL-1 cells cultured on extracellular matrix in a manner indicative of extra-villous trophoblast. Dot-blot immunoassays and ELISA indicated that CSF-1 was secreted by TCL-1 cells, at levels comparable to primary trophoblast cells and BeWo choriocarcinoma (trophoblast tumour) cells. Reverse transcriptase-polymerase chain reaction analysis confirmed the presence in TCL-1 cells of CSF-1 receptor mRNA (c-fms gene product), indicating that the components of a potential autocrine loop were present in these cells. Proliferation of TCL-1 cells was not affected by the addition of exogenous CSF-1 but was elevated in response to treatment with a CSF-1 neutralizing antibody. The immortalized cell line, TCL-1, provides a potential model in which to investigate regulation of growth and differentiation of trophoblast cells in vitro.
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PMID:Partial characterization of an immortalized human trophoblast cell-line, TCL-1, which possesses a CSF-1 autocrine loop. 917 33

The osteopetrotic (op/op) mouse, deficient in biologically active colony stimulating factor 1 (CSF-1), was used to examine the role of microglia in chemical-induced trauma. Op/op mice and normal phenotype littermates (non-op/op) received an acute i.p. injection of the hippocampal toxicant, trimethyltin hydroxide (TMT; 1.5 or 2.0 mg/kg). At 2.0 mg/kg, both mice displayed severe degeneration of dentate granule neurons. At 1.5 mg/kg, non-op/op mice showed a limited punctate pattern of neuronal death while op/op mice showed prominent neuronal death. TMT-induced astrocyte reactivity was similar in both groups. RNase protection assays were conducted on hippocampal tissue at 24 hr post-TMT. Elevations were seen in mRNA levels for the host response genes: intercellular cell adhesion molecule (ICAM-1; non-op/op 80%, op/op 85%), the protease inhibitor EB22 (non-op/op 60%, op/op 300%), and glial fibrillary acidic protein (GFAP; non-op/op 300%, op/op 480%) within 24 hr. Macrophage-1 antigen (Mac-1) mRNA levels were lower in all op/op mice and were not induced by TMT exposure. Macrophage inflammatory protein (MIP)-1alpha and MIP-1beta mRNA levels were elevated in non-op/op mice while mRNA levels for interferon inducible protein (IP-10) and monocyte chemoattractant protein (MCP-1) were elevated in op/op mice. Tumor necrosis factor alpha (TNFalpha) mRNA levels were significantly elevated in both non-op/op (100%) and op/op (600%) mice. TNFbeta mRNA levels in op/op mice were elevated 200% and interleukin 1alpha (IL-1alpha) 150%. Reverse transcriptase polymerase chain reaction (RT-PCR) showed a TMT-induced elevation in INFalpha and INFbeta mRNA levels and no elevation of INFgamma. mRNA levels of the CSF-1 receptor, c-fms, were unaltered.
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PMID:Chemical-induced hippocampal neurodegeneration and elevations in TNFalpha, TNFbeta, IL-1alpha, IP-10, and MCP-1 mRNA in osteopetrotic (op/op) mice. 1100 96

Peritoneal dialysis requires large solution volumes that increase abdominal girth and stretch the mesothelial cells of the abdominal wall. To address the hypothesis that stretch stimulates those cells to increase synthesis and production of inflammatory cytokines, we grew MeT-5A human mesothelial cells to confluence and placed the cells in growth arrest on BioFlex Collagen membranes (Flexcell International Corporation, Hillsborough, NC, U.S.A.). After 48 hours, cells were either left stationary (STA) or cycled using a 3000T system (Flexcell International Corporation) with a sinusoidal stretch (STR) frequency of 10 cycles per minute and an amplitude of 30%. The supernatant and cells of individual wells were removed at 0, 4, 12, 24, 48, 72, and 96 hours. Supernatant was assayed by ELISA for transforming growth factor beta (TGF-beta), interleukin 6 (IL-6), and vascular endothelial growth factor (VEGF). After trypsinization, the total number of viable cells in each well was estimated from the lack of trypan blue staining. Total RNA from the cells was extracted, and real-time reverse-transcriptase polymerase chain reaction was used to determine messenger RNA (mRNA) for IL-6, TGF-beta, VEGF, TGF-beta receptors 2 and 3 (TGF-beta-R2, -R3), kinase insert domain receptor (KDR), and FMS-related tyrosine kinase 1 (Flt1). Because of decline of cell numbers and viability, results for STR were compared with those for STA at each time interval up to 72 hours. The mRNA for TGF-beta, VEGF, TGF-beta-R3, and KDR were significantly higher in the STR group throughout the 72 hours, and STR IL-6 mRNA declined nonsignificantly. Normalized to the number of viable cells, supernatant IL-6, TGF-beta, and VEGF were not significantly different between the groups. We conclude that mechanical stress from mesothelial stretch does not enhance mesothelial cell secretion oflL-6, TGF-f, or VEGF, but does increase expression ofTGF-P, VEGF, and their corresponding cell receptors TGF-f-R3 and KDR.
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PMID:Stretch of human mesothelial cells increases cytokine expression. 2331 Dec 5