Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:2.7.7.6 (RNA polymerase)
34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this study, we investigated the expression of granulocyte colony-stimulating factor (G-CSF), G-CSF mRNA, G-CSF receptor mRNA in glioma cell lines, G-CSF in glioma cyst fluids, and the effect of recombinant G-CSF on the proliferation of glioma cells. First, to determine whether G-CSF is produced by glioma cells, we analyzed for the presence of G-CSF by ELISA in supernatants from glioma cell lines. G-CSF was detected in six of fourteen glioma cell lines constitutively, and, after stimulation with tumor necrosis factor-alpha (TNF-alpha), G-CSF was detected in four of eight cell lines which did not produce G-CSF constitutively. Then, we analyzed the expression of G-CSF mRNA by reverse-transcriptase polymerase chain reaction (RT-PCR) in six cell line, of which two produced G-CSF constitutively and three produced G-CSF only after stimulation with TNF-alpha. G-CSF mRNA was detected in all cell lines studied. To determine whether G-CSF was produced in vivo, we analyzed the presence of G-CSF by ELISA in five glioma cyst fluids, but G-CSF was not detected in any. We also analyzed the effect of G-CSF on the proliferation of glioma cells. The growth of glioma cells alone was not different from that of glioma cells incubated with recombinant G-CSF. In addition, we analyzed the presence of G-CSF receptor mRNA in glioma cells by RT-PCR; G-CSF receptor mRNA was not detected.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:[The expression of granulocyte colony-stimulating factor in malignant gliomas]. 753 27

In this study we have examined hFc gamma RI expression during myelopoiesis. Normal bone marrow (BM) cells were found to express hFc gamma RI up to the metamyelocyte stage. A different Fc gamma RI expression pattern was observed in an in vitro model of myelopoiesis. Purified CD34-positive BM cells, cultured for 12 to 14 days with granulocyte colony-stimulating factor (G-CSF), differentiate into a population of mature granulocytic cells. In these cultures, in which hFc gamma RI was virtually absent on the initial CD34-positive BM cells, hFc gamma RI was strongly induced by G-CSF after only 5 days. During final maturation the cells remained hFc gamma RI positive. This expression was confirmed functionally by antibody-sensitized erythrocytes (EA)-rosette assays. Moreover, the mature myeloid cells were found to express mRNA encoding for hFc gamma RI, whereas reverse-transcriptase polymerase chain reaction analysis showed that both hFc gamma RIA and hFc gamma RIB genes were expressed. In contrast, on peripheral blood (PB) polymorphonuclear neutrophil leukocytes (PMN) the in vitro effect of G-CSF as to hFc gamma RI induction was limited. Therefore, we conclude that, with respect to hFc gamma RI expression on PMN, G-CSF acts on myeloid precursor cells rather than on mature cells. This conclusion could be strengthened by in vivo administration of a single dose of G-CSF to a healthy volunteer. After a 12-hour lag time, hFc gamma RI expressing PMNs were detected in the peripheral blood. This study shows that hFc gamma RI is an early myeloid differentiation marker that is lost during normal final maturation. However, committed myeloid progenitor cells can be strongly induced by G-CSF to express hFc gamma RI, ultimately resulting in mature granulocytic cells expressing the high-affinity receptor for IgG. This expression may have important consequences for the functional capacity of these cells.
...
PMID:Granulocyte colony-stimulating factor induces hFc gamma RI (CD64 antigen)-positive neutrophils via an effect on myeloid precursor cells. 768 Sep 17

Reverse transcriptase-polymerase chain reaction showed that interleukin 3, IL-4, IL-5, IL-6, interferon-gamma and stem cell factor mRNA expression were higher in 15-deoxyspergualin-treated spleen cells than in control spleen cells. Increased IL-2 and IFN-gamma mRNA expression were observed in 15-deoxyspergualin-treated bone marrow cells. On the other hand, increased platelet counts in BALB/c-->C3H/He bone marrow chimeras were observed from days 20 to 33 in our previous work, when they were treated with 15-deoxyspergualin from days 14 to 25. In contrast, marked leukocytopenia and anemia were simultaneously observed, although a marked leukocytosis and a rapid recovery of anemia were observed on day 33 and thereafter. To analyze effects of 15-deoxyspergualin on hematopoiesis and the immune system, we examined mRNA expression in bone marrow and spleen cells from BALB/c-->C3H/He bone marrow chimeras treated with 15-deoxyspergualin from days 14 to 25. Reverse transcriptase-polymerase chain reaction showed that IL-3, IL-4, IL-6, stem cell factor, granulocyte colony-stimulating factor, and granulocyte/macrophage colony-stimulating factor mRNA expression were higher in 15-deoxyspergualin-treated chimeras than in control chimeras, indicating that these cytokines are responsible for an enhancement of hematopoiesis. It was conceivable that IL-6 supported thrombopoiesis in concert with other cytokines. On the contrary, increased IFN-gamma, IL-2, IL-3, IL-4, and IL-10 mRNA expression may play an immunosuppressive role in vivo.
...
PMID:Effects of 15-deoxyspergualin in vitro and in vivo on cytokine gene expression. 797 17

Remission marrow from patients with BCR-ABL+ acute lymphoblastic leukemia (ALL) achieving clinical remission (CR) after induction or consolidation chemotherapy according to the German multicenter adult ALL (GMALL) protocol showed high titers of residual BCR-ABL+ cells. Therefore, we initiated a pilot study to monitor circulating BCR-ABL+ cells and to collect, purge, and autograft peripheral blood stem cells (PBSC) in these patients. After GMALL 05/93 high-risk phase II of induction chemotherapy (high-dose AraC 3 g/m2 x 8 does and mitoxantrone 10 mg/m2 x 3 doses), patients received 5-10 micrograms/kg subcutaneous recombinant human granulocyte colony-stimulating factor (rhG-CSF) daily. Mobilized CD34+ cells peaked between 20 and 26 days after starting chemotherapy at 4.8-75.6 (median 10.8) x 10(4)/mL peripheral blood (PB) (n = 5). Patients treated with additional chemotherapy cycles failed to mobilize adequate numbers of CD34+ cells. PB stem cells (PBSC) were purged using a cocktail of CD10, CD19, and AB4 monoclonal antibodies (mAbs) coupled to immunomagnetic beads (IMB). The median recoveries of total nucleated cells (TNC) and CD34+ cells after mAb/IMB purging were 84 and 81%. The peak numbers of CD34+ cells collected in a single leukapheresis were median 8.6 x 10(6)/kg pre- and 5.2 x 10(6)/kg postpurge (n = 4). The absolute prepurge CD19+ cells were as low as median 2.7 (range 1.4-19) x 10(6) per leukapheresis. Residual BCR-ABL+ cells in unpurged leukapheresis products were assessed by limiting-log10-dilution nested reverse-transcriptase polymerase chain reaction (RT-PCR) as one in 10(5) to one in 10(6) normal cells and were consistently undetectable in all purged PBSC autografts. We conclude that sufficient numbers of CD34+ cells for PBSCT can be collected after phase II but not at later stages of the GMALL 05/93 high risk protocol; PBSC grafts are 3 log less contaminated with residual BCR-ABL+ cells compared to an historical series of 13 autologous BM grafts; and purging of PBSC with mAb/IMB is feasible with minor loss of CD34+ cells and abolished BCR-ABL signals in the grafts.
...
PMID:Purging of peripheral blood stem cells yields BCR-ABL-negative autografts in patients with BCR-ABL-positive acute lymphoblastic leukemia. 854 55

We investigated the expression of granulocyte colony-stimulating factor (G-CSF), G-CSF mRNA, and G-CSF receptor mRNA in astrocytoma cell lines, G-CSF in astrocytoma cyst fluid, and the effect of recombinant G-CSF on the proliferation of astrocytoma cells in vitro and in vivo. We first examined supernatants from astrocytoma cell lines for the presence of G-CSF by ELISA. G-CSF was expressed by 6 of 14 astrocytoma cell lines constitutively, and, was detected after stimulation with tumor necrosis factor-alpha (TNF-alpha) in four of eight cell lines which did not produce G-CSF constitutively. G-CSF mRNA was detected by reverse-transcriptase polymerase chain reaction (RT-PCR) in all cell lines studied, suggesting that astrocytoma cells have the potential to produce G-CSF. We also analyzed the presence of G-CSF by ELISA in five astrocytoma cyst fluids. G-CSF was detected in one case. Although, in vitro study, the growth of glioma cells was not affected by rG-CSF, in a mouse model, the administration of G-CSF significantly shortened the time to tumor appearance and accelerated tumor growth. These data suggest that G-CSF has a stimulatory effect on the proliferation of astrocytoma cells in vivo through the mediation of host factors.
...
PMID:Granulocyte colony-stimulating factor (G-CSF) production by astrocytoma cells and its effect on tumor growth. 869 23

The receptor for the gene product of the obesity gene, leptin, was recently reported to be expressed on murine and human hematopoietic progenitor cells. Therefore, we studied the expression of the leptin receptor, OB-R, in normal myeloid precursors, human leukemia cell lines, and primary leukemic cells using reverse-transcriptase polymerase chain reaction. In normal hematopoiesis, OB-R was expressed in CD34(+) cells. Normal promyelocytes (CD34(-)33(+) and CD34(-)13(+)) expressed only very low levels of the short, presumably nonsignaling isoform. Both the long and short isoforms of OB-R were expressed in 10 of 22 samples from patients with newly diagnosed primary or secondary acute myeloid leukemia (AML), with a higher incidence of the long isoform in primary AML (87.6% v 28.6%; P =.01). The incidence of OB-R expression was higher in recurrent than in newly diagnosed AML (P <.001), and samples from four patients with refractory AML showed strong expression of both isoforms. Both OB-R isoforms were also expressed in newly diagnosed and recurrent acute promyelocytic leukemia cells but were essentially absent in samples of chronic or acute lymphocytic leukemia. In vitro growth of myeloid leukemic cell lines and of blasts from 14 primary AMLs demonstrated that recombinant human leptin alone induced low level proliferation, significantly (P <.05) increased proliferation induced by recombinant human granulocyte colony-stimulating factor, interleukin 3, and stem cell factor in a subset of AML and increased colony formation (P <.005). Also, leptin reduced apoptosis induced by cytokine withdrawal in MO7E and TF-1 cells. Serum leptin levels correlated only with body mass index (P <. 001) and gender (P =.03). Results confirm the reported expression of leptin receptor in normal CD34(+) cells and demonstrate the frequent expression of leptin receptors in AML blasts. While normal promyelocytes lack receptor expression, leukemic promyelocytes express both isoforms. We also demonstrate proliferative effects of leptin alone and in combination with other physiologic cytokines, and anti-apoptotic properties of leptin. These findings could have implications for the pathophysiology of AML.
...
PMID:Expression and function of leptin receptor isoforms in myeloid leukemia and myelodysplastic syndromes: proliferative and anti-apoptotic activities. 1002 96

Legionella pneumophila causes community-acquired pneumonia with high mortality, but little is known about its interaction with the alveolar epithelium. The aim of this study was to investigate whether L. pneumophila infection of lung epithelial cells (A549) resulted in pro-inflammatory activation. L. pneumophila infection induced liberation of interleukin (IL)-2, -4, -6, -8 and -17, monocyte chemoattractant protein-1, tumour necrosis factor-alpha, IL-1beta, interferon-gamma and granulocyte colony-stimulating factor, but not of IL-5, -7, -10, -12 (p70) or -13 or granulocyte-macrophage colony-stimulating factor. The present study focused on IL-8 and found induction by L. pneumophila strains 130b, Philadelphia 1, Corby and, to a lesser extent, JR32. Knockout of dotA, a central gene involved in type IVB secretion, did not alter IL-8 induction, whereas lack of flagellin significantly reduced IL-8 release by Legionella. Moreover, p38 mitogen-activated protein kinase (MAPK) was activated and kinase inhibition reduced secretion of induced cytokines, with the exception of IL-2 and granulocyte colony-stimulating factor. In contrast, inhibition of the MAPK kinase 1/extracellular signal-regulated kinase pathway only reduced the expression of a few cytokines. L. pneumophila also induced binding of nuclear factor-kappaB subunit RelA/p65 and RNA polymerase II to the il8 promoter, and a specific inhibitor of the inhibitor of nuclear factor-kappaB complex dose-dependently lowered IL-8 expression. Taken together, Legionella pneumophila activated p38 mitogen-activated protein kinase- and nuclear factor-kappaB/RelA pathway-dependent expression of a complex pattern of cytokines by human alveolar epithelial cells, presumably contributing to the immune response in legionellosis.
...
PMID:Legionella pneumophila-induced NF-kappaB- and MAPK-dependent cytokine release by lung epithelial cells. 1697 6

Neoangiogenesis is a key process in the initial phase of ligament healing. Adult human circulating CD34+ cells, an endothelial/hematopoietic progenitor-enriched cell population, have been reported to contribute to neoangiogenesis; however, the therapeutic potential of CD34+ cells for ligament healing is still unclear. Therefore, we performed a series of experiments to test our hypothesis that ligament healing is supported by CD34+ cells via vasculogenesis. Granulocyte colony-stimulating factor-mobilized peripheral blood (GM-PB) CD34+ cells with atelocollagen (CD34+ group), GM-PB mononuclear cells (MNCs) with atelocollagen (MNC group), or atelocollagen alone (control group) was locally transplanted after the creation of medial collateral ligament injury in immunodeficient rats. Reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemical staining at the injury site demonstrated that molecular and histological expression of human-specific markers for endothelial cells was higher in the CD34+ group compared with the other groups at week 1. Endogenous effect, assessed by capillary density and mRNA expression of vascular endothelial growth factor, was significantly higher in CD34+ cell group than the other groups. In addition to the observation that, as assessed by real-time RT-PCR, gene expression of ligament-specific marker was significantly higher in the CD34+ group than in the other groups, ligament healing assessed by macroscopic, histological, and biomechanical examination was significantly enhanced by CD34+ cell transplantation compared with the other groups. Our data strongly suggest that local transplantation of circulating human CD34+ cells may augment the ligament healing process by promoting a favorable environment through neovascularization.
...
PMID:Administrations of peripheral blood CD34-positive cells contribute to medial collateral ligament healing via vasculogenesis. 1819 36

Inflammatory activation of the endothelium by Chlamydophila pneumoniae infection has been implicated in the development of chronic vascular lesions and coronary heart disease by seroepidemiological and animal studies. We tested the hypothesis that C. pneumoniae induced inflammatory gene expression is regulated by Rho-GTPase-related histone modifications. C. pneumoniae infection induced the liberation of proinflammatory interleukin-6, interleukin-8, granulocyte colony-stimulating factor, macrophage inflammatory protein-1beta, granulocyte/macrophage colony-stimulating factor, and interferon-gamma by human endothelial cells. Cytokine secretion was reduced by simvastatin and the specific Rac1 inhibitor NSC23766 but was synergistically enhanced by inhibitors of histone deacetylases trichostatin A and suberoylanilide hydroxamic acid. Infection of endothelial cells with viable C. pneumoniae, but not exposure to heat-inactivated C. pneumoniae or infection with C. trachomatis, induced acetylation of histone H4 and phosphorylation and acetylation of histone H3. Pretreatment of C. pneumoniae-infected cells with simvastatin or NSC23766 reduced global histone modifications as well as specific modifications at the il8 gene promoter, as shown by chromatin immunoprecipitation. Reduced recruitment of nuclear factor kappaB p65/RelA as well as of RNA polymerase II was observed in statin-treated cells. Taken together, Rac1-mediated histone modifications seem to play an important role in C. pneumoniae-induced cytokine production by human endothelial cells.
...
PMID:Simvastatin reduces Chlamydophila pneumoniae-mediated histone modifications and gene expression in cultured human endothelial cells. 1843 97

The functions of immune cells in brain metastases are unclear because the brain has traditionally been considered "immune privileged." However, we found that a subgroup of immunosuppressive neutrophils is recruited into the brain, enabling brain metastasis development. In brain metastatic cells, enhancer of zeste homolog 2 (EZH2) is highly expressed and phosphorylated at tyrosine-696 (pY696)-EZH2 by nuclear-localized Src tyrosine kinase. Phosphorylation of EZH2 at Y696 changes its binding preference from histone H3 to RNA polymerase II, which consequently switches EZH2's function from a methyltransferase to a transcription factor that increases c-JUN expression. c-Jun up-regulates protumorigenic inflammatory cytokines, including granulocyte colony-stimulating factor (G-CSF), which recruits Arg1⁺- and PD-L1⁺ immunosuppressive neutrophils into the brain to drive metastasis outgrowth. G-CSF-blocking antibodies or immune checkpoint blockade therapies combined with Src inhibitors impeded brain metastasis in multiple mouse models. These findings indicate that pY696-EZH2 can function as a methyltransferase-independent transcription factor to facilitate the brain infiltration of immunosuppressive neutrophils, which could be clinically targeted for brain metastasis treatment.
...
PMID:Blocking immunosuppressive neutrophils deters pY696-EZH2-driven brain metastases. 3246 34


1

---