Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The conference, organized by Profs. Mitrou, Bergmann (Frankfurt), Huber (Mainz) and Niederle (Leverkusen), concentrated almost exclusively on the role of cytokines in cancer. The majority of presentations concerned IFN-alpha, IL 2 or TNF-alpha, but G-CSF, GM-CSF, IL 4, IL 10 and TGF-beta were not neglected. Presentations achieved a laudable balance between basic science and clinically oriented studies. The present report emphasizes the clinical aspects; proceedings of the entire meeting will be published by S. Karger AG, Basel.
Mol Biother 1992 Dec
PMID:The role of cytokines in tumor immunotherapy. Report on the 2nd Frankfurt International Cytokine Symposium 25-27 June 1992, Frankfurter Hof, Frankfurt, Germany. 136 64

We examined expression and cytotoxic triggering capability of the three Fc receptors for IgG (Fc gamma R) on human monocytes, PMNs and myeloid cell lines after in vitro culture with various cytokines. Fc gamma R expression was evaluated using specific anti-Fc gamma R monoclonal antibodies (mAb). The cytotoxic capability of each Fc gamma R was examined after the effector cells were treated with the recombinant cytokines IFN-gamma. TNF alpha, GM-CSF, G-CSF, M-CSF, IL-1, IL-2, IL-3, IL-4, or IL-6. Hybridoma cell lines (HC) bearing antibody directed to Fc gamma RI (HC 32), Fc gamma RII (HC IV.3) or Fc gamma RIII (HC 3G8) were used as targets, as were chicken erythrocytes (CE) sensitized with heteroantibodies composed of anti-Fc gamma R mAbs (32, IV.3, 3G8) linked to anti-CE antibody. Only IFN-gamma treatment significantly increased Fc gamma R expression and then only Fc gamma RI. IFN-gamma dramatically up-regulated Fc gamma RI expression on all cells tested. However, ADCC was enhanced by treatment with a number of cytokines other than IFN-gamma. GM-CSF, TNF, and IFN-gamma treatment enhanced killing of HC 32 and HC IV.3 by in vitro cultured monocytes. G-CSF treatment enabled PMNs to kill HC through Fc gamma RII, whereas PMN killing of HC through Fc gamma RIII could not be induced by any of the cytokines studied. Although only IFN-gamma treatment increased ADCC of CE by monocytes, GM-CSF treatment as well as IFN-gamma treatment augmented ADCC of CE by PMNs. In addition to IFN-gamma treatment, IL-6 treatment enabled U937 cells to lyse CE. Whereas IFN-gamma-treated U937 cells killed CE through both Fc gamma RI and Fc gamma RII, IL-6-treated U937 cells killed CE only through Fc gamma RI. In addition to IFN-gamma treatment, G-CSF treatment enabled HL-60 cells to lyse CE through both Fc gamma RI and Fc gamma RII. These results demonstrate that although IFN-gamma appears unique in regulating Fc gamma R expression on myeloid cells, cytokines other than IFN-gamma affect ADCC by these cells in a receptor-specific manner.
Mol Immunol 1990 Jan
PMID:The effect of cytokines on the expression and function of Fc receptors for IgG on human myeloid cells. 213 46

A conserved DNA sequence element, termed cytokine 1 (CK-1), is found in the promoter regions of many hemopoietic growth factor (HGF) genes. Mutational analyses and modification interference experiments show that this sequence specifically binds a nuclear transcription factor, NF-GMa, which is a protein with a molecular mass of 43 kilodaltons. It interacts with different affinities with the CK-1-like sequence from a number of HGF genes, including granulocyte macrophage colony-stimulating factor (GM-CSF), granulocyte (G)-CSF, interleukin 3 (IL-3), and IL-5. We show here that the level of NF-GMa binding is induced in embryonic fibroblasts by tumor necrosis factor-alpha (TNF-alpha) treatment and that the CK-1 sequence from the G-CSF gene is a TNF-alpha-responsive enhancer in these cells. The NF-GMa protein is distinct from another TNF-alpha-responsive transcription factor, NF-kappa B, by several criteria. Firstly, several NF-kappa B-binding sites, although having sequence similarity with the CK-1 sequence, cannot compete efficiently for NF-GMa binding to CK-1. Secondly, the CK-1 sequence from both G-CSF and GM-CSF does not respond to phorbol ester treatment as would an NF-kappa B-binding element. These results demonstrate that NF-GMa is a novel transcription factor inducible by TNF-alpha and binds to a common element in HGF gene promoters.
Mol Cell Biol 1990 Jun
PMID:A novel tumor necrosis factor-responsive transcription factor which recognizes a regulatory element in hemopoietic growth factor genes. 234 64

Activation of T cells by an antigen, a mitogen, or a combination of a phorbol ester (12-O-tetradecanoylphorbol-13-acetate [TPA]) and a calcium ionophore (A23187) leads to induction of a set of lymphokine genes. Treatment of human T-cell leukemia line Jurkat by a mitogen or p40x, a transactivator protein encoded by human T-cell leukemia virus type I, activates many transfected lymphokine genes in a transient transfection assay. To study the mechanism of lymphokine gene induction, we examined the effects of mitogen stimulation and p40x on the gene for the mouse granulocyte-macrophage colony-stimulating factor (GM-CSF) in Jurkat cells. Deletion and mutation analyses showed that the 5'-flanking region of the gene for the GM-CSF is composed of two types of regulatory elements. One sequence, located at positions -95 to -73, determines response to stimulation by either TPA-A23187 or p40x. This region contains conserved lymphokine element 2, which appears in the gene for interleukin 3 (IL-3) and is followed by a GC-rich stretch. This GC-rich stretch alone specifies inducible response to p40x but not to TPA-A23187. Another sequence, located at positions -113 to -96 upstream of a TATA-like sequence, mediates inducible response to p40x but not to TPA-A23187. This sequence includes conserved lymphokine element 1, which appears in several lymphokine-cytokine genes, such as those for IL-3, G-CSF, and IL-2. We previously showed that the simian virus 40 early region promoter was also induced by a mitogen or p40x in Jurkat cells. Deletion analysis showed that the minimum region require for stimulation by both signals are identical. These results, which indicate that p40(x) stimulates transcription of the gene for the GM-CSF or the simian virus 40 early region promoter through the same DNA element or an overlapping DNA element required for induction by a mitogen, lend further support to the notion that p40(x) can exert its function by activating a component(s) of the T-cell signal transduction pathway which is activated by an antigen or a mitogen.
Mol Cell Biol 1988 Dec
PMID:T-cell activation signals and human T-cell leukemia virus type I-encoded p40x protein activate the mouse granulocyte-macrophage colony-stimulating factor gene through a common DNA element. 285 2

We have previously shown that granulocyte (G-CSF) and granulocyte/macrophage (GM-CSF) colony-stimulating factors present in human bronchial epithelial cell conditioned medium (HBEC-CM) suppress apoptosis in neutrophils. In this study, we demonstrate that HBEC-CM also induces increased expression of manganese superoxide dismutase (MnSOD) and heat shock protein 70 (HSP70) in neutrophils. However, treatment of neutrophils with recombinant GM-CSF and G-CSF, which suppressed apoptosis to equivalent degrees, did not induce MnSOD or HSP 70. Thus, we conclude that induction of stress proteins is associated with, but not necessary for, suppression of apoptosis.
Am J Respir Cell Mol Biol 1994 May
PMID:Manganese superoxide dismutase and heat shock protein 70 are not necessary for suppression of apoptosis in human peripheral blood neutrophils. 751 9

Histamine and recombinant granulocyte colony-stimulating factor (rG-CSF) stimulated the differentiation of murine myeloblasts and promyelocytes to mature neutrophils. In connection with this, myeloperoxidase activity of these progenitor cells was decreased by either histamine or rG-CSF treatment. After pretreatment with histamine at 1 microM, both differentiation and the decrease in myeloperoxidase activity of myeloblasts and promyelocytes induced by rG-CSF were significantly augmented. Binding assays using 125I-labeled rG-CSF showed that the number of rG-CSF binding sites on the surface of neutrophil progenitor cells increased after histamine treatment. The histamine-induced increase in rG-CSF binding appeared to be definitely through H2 receptors. Furthermore, the increase in rG-CSF binding sites due to histamine treatment seemed to take place in association with the externalization of G-CSF receptors, because 1) the binding increase was observed in the presence of cycloheximide, 2) no concomitant increase in [3H]leucine uptake was elicited, and 3) colchicine and cytochalasin D effectively prevented the increase in rG-CSF binding due to histamine. In neutrophil progenitors, cAMP contents increased very rapidly and significantly after either histamine or rG-CSF treatment. Moreover, dibutyryl-cAMP increased rG-CSF binding to neutrophil progenitor cells in a dose-dependent fashion. However, when progenitor cells were pretreated with protein kinase A inhibitors, the histamine-induced increase in rG-CSF binding was remarkably decreased. This result seems to indicate that the stimulatory effects of histamine on rG-CSF binding to progenitor cells are intimately related to the cAMP-protein kinase A system in neutrophil progenitors. Moreover, c-myc mRNA expression in neutrophil progenitors was markedly reduced by either histamine or rG-CSF treatment. It was concluded that rG-CSF-induced differentiation of murine neutrophil progenitors was augmented by histamine pretreatment mainly due to an increase in rG-CSF receptors on these cells and this increase might be related to the externalization of rG-CSF receptors.
Mol Pharmacol 1994 May
PMID:Reinforcement effect of histamine on the differentiation of murine myeloblasts and promyelocytes: externalization of granulocyte colony-stimulating factor receptors induced by histamine. 751 13

The secondary structure and backbone dynamics of the cytokine, human granulocyte colony-stimulating factor (hG-CSF) have been determined by heteronuclear nuclear magnetic resonance (NMR) techniques. Virtually complete NH, C alpha H, C beta H 15N, 13C alpha, and 13C beta assignment of the 175-residue recombinant protein, methionyl-[Cys-17-Ser]-hG-CSF, was achieved by use of three-dimensional (3D) heteronuclear 1H-15N and triple-resonance 1H-15N-13C experiments. Spectra recorded at 750 MHz aided the assignment of severely overlapped regions. The structures of G-CSF from several species have recently been determined by X-ray diffraction [Hill, C. P., Osslund, T. D., & Eisenberg, D. (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 5167-5171; Lovejoy, B., Cascio, D., & Eisenberg, D. (1993) J. Mol. Biol. 234, 640-653]. Like several cytokines, hG-CSF has a four-helix topology (A-D) with overhand loop connections, but with an additional helical segment (A') identified in the connection between helix A and helix B. The solution-state determination of the secondary structure is based on short- and medium-range NOEs, backbone J-couplings, and NH exchange data and is corroborated by 13C alpha secondary shifts. The helices are defined as follows: A, 10-38; A',44-53; B, 71-91; C, 102-123; D, 143-172. The dynamics of the amide backbone resonances, investigated using 1H-15N heteronuclear NMR, indicate a rigid protein core with some increased mobility in the AB loop and more pronounced mobility in the CD loop.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Secondary structure and backbone dynamics of human granulocyte colony-stimulating factor in solution. 751 82

To evaluate the physiological role of G-CSF following surgery, we measured the serum levels of immunoreactive IL-6 and G-CSF sequentially in nine patients after major elective thoracoabdominal surgery for esophageal carcinoma. Both G-CSF and IL-6 levels reached their maxima at the first postoperative day and decreased thereafter. There was a significant correlation between serum G-CSF (y) and IL-6 (x) levels (y = 3.273x + 3.991; r = 0.787, n = 78, p < 0.001). In the case that developed aspiration pneumonia and ARDS at the second postoperative day, the measured G-CSF level was less than half the predicted value. The relationship between serum G-CSF and IL-6 levels supports the central role of G-CSF as the host defense response modifier and, thus, low G-CSF levels in the circulation is one reason for the immunodeficient state after major surgery.
Res Commun Mol Pathol Pharmacol 1995 Mar
PMID:Changes in serum granulocyte colony-stimulating factor (G-CSF) and interleukin 6 (IL-6) after surgical intervention. 754 36

Using two different cell systems, we show that the cytoplasmic domain of the granulocyte-colony-stimulating factor receptor (G-CSFR) may be composed of at least two functional regions. The first, within the membrane-proximal 57 amino acids, is absolutely required to deliver a proliferative signal. This region contains two sequence motifs conserved between members of the hematopoietin receptor family. The second functional region resides between amino acids 57 and 96. This region is required for the induction of acute-phase plasma protein gene expression when the G-CSFR is transfected into human hepatoma cell lines. The G-CSFR-transfected hepatoma cells respond to G-CSF by increasing the production of the same set of plasma proteins as stimulated by interleukin-6, suggesting that the two cytokines share a common signal transduction pathway.
Mol Cell Biol 1993 Apr
PMID:Distinct regions of the human granulocyte-colony-stimulating factor receptor cytoplasmic domain are required for proliferation and gene induction. 768 Nov 46

The receptor for leukemia inhibitory factor (LIFR), in combination with the signal-transducing subunit for interleukin-6-type cytokine receptors, gp130, and LIF, activates transcription of acute-phase plasma protein genes in human and rat hepatoma cells and the vasoactive intestinal peptide gene in a human neuroblastoma cell line. To identify the regions within the cytoplasmic domain of LIFR that initiate signal transduction independently of gp130, we constructed a chimeric receptor by linking the extracellular domain of the granulocyte colony-stimulating factor receptor (G-CSFR) to the transmembrane and cytoplasmic domain of human LIFR. The function of the chimeric receptor protein in transcriptional activation was assessed by G-CSF-mediated stimulation of cotransfected cytokine-responsive reporter gene constructs in hepatoma and neuroblastoma cells. By using the full-length cytoplasmic domain and mutants with progressive carboxy-terminal deletions, internal deletions, or point mutations, we identified the first 150 amino acid residues of LIFR as the minimal region necessary for signaling. The signaling reaction appears to involve a cooperativity between the first 70-amino-acid region containing the two sequence motifs conserved among hematopoietin receptors (box 1 and box 2) and a critical sequence between residues 141 and 150 (box 3). Analogous analyses of the cytoplasmic domains of G-CSFR and gp130 indicated similar arrangements of functional domains in these receptor subunits and the requirement of a box 3-related motif for signaling.
Mol Cell Biol 1994 Jan
PMID:Multiple regions within the cytoplasmic domains of the leukemia inhibitory factor receptor and gp130 cooperate in signal transduction in hepatic and neuronal cells. 826 82


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