Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04141 (granulocyte-macrophage colony-stimulating factor)
 6,790 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human interleukin 3 (IL-3) is a multipotential cytokine that supports the growth of early hematopoietic progenitors and promotes their response to other, later-acting cytokines. We found that IL-3 was able to induce the expression of interleukin 2 (IL-2) receptor (IL-2R) (CD25) on a subset of early myeloid cells in normal human bone marrow that had been first depleted of mature hematopoietic cells and E-rosette-positive T cells by treatment with soybean lectin and sheep erythrocytes (SBA-E-BM). Immunofluorescence analysis revealed that the CD25+ cells were contained almost entirely within the lymphoblastoid gate of the IL-3-cultured marrow. CD25 was undetectable on freshly isolated marrow and less than 10% CD25+ cells could be detected following liquid culture at 37 degrees C in the presence of 10% human serum, 10% fetal calf serum, or under serum-free conditions. Addition of IL-3 (100 U/ml) significantly increased the expression of CD25 to 37%, 31%, and 24%, respectively. CD25 could also be induced by granulocyte-macrophage colony-stimulating factor (GM-CSF), but no IL-2R was detectable following exposure to granulocyte colony-stimulating factor (G-CSF), macrophage colony-stimulating factor (M-CSF), interleukin 1 (IL-1), interleukin 4 (IL-4), or IL-2. Expression of CD25 was dependent on the dose of IL-3 or GM-CSF added and was maximal within 24 h of exposure. Two-color immunofluorescence analysis demonstrated that CD25 was not expressed by cells of lymphoid lineage or by mature monocytes, but rather was present on cells that coexpressed CD13, CD33, CD34, MY8, and HLA-DR, and that lacked CD14 or CD11b, thus placing the CD25+ cells at or near the myeloblast stage of differentiation. An identical phenotype was found for CD25+ cells induced by GM-CSF. Cycloheximide completely inhibited the IL-3-induced expression of CD25, indicating the necessity for protein synthesis, and although most of the CD25+ cells were in G0/G1 phase, 25% of the cells were in S or G2M phase, indicating that receptor expression was not cell-cycle dependent. The p75 chain of IL-2R was not detected on the CD25+ cells. IL-3 was also found to directly induce CD25 in greater than 46% of SBA-E-BM enriched for CD34+ cells by panning. Consistent with the expression of only p55 IL-2R, the functional activity of IL-2 on enriched CD34+ cells exposed to IL-3 could not be demonstrated in either granulocyte-macrophage colony-forming unit (CFU-GM) assays or proliferation assays.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Recombinant interleukin 3 induces interleukin 2 receptor expression on early myeloid cells in normal human bone marrow. 137 65

The effect of parathyroid hormone (PTH) on immunoglobulin (Ig) production and proliferation in the human B-cell lines CBL, SKW, and CESS was studied. PTH inhibited Ig production from all the B-cell lines in a dose-dependent manner during 5 days of culture. As little as 0.1 ng/ml was inhibitory. PTH also inhibited Ig production from cell lines stimulated by vasoactive intestinal peptide (VIP), interleukin 2 (IL-2), and IL-6. This inhibition was not due to decreased cell growth since proliferation was not affected and cell viability was always greater than 98%. In contrast to PTH, inactivated PTH or triiodothyronine failed to affect Ig production. Inhibition by PTH was blocked by anti-PTH serum, but not by control serum. Of the various cytokines tested, IL-4 reduced the PTH-induced inhibition of Ig production, whereas other cytokines, including IL-1 beta, IL-3, IL-5, interferon alpha (IFN-alpha), IFN-gamma, and granulocyte-macrophage colony-stimulating factor (GM-CSF), failed to do so. The reducing effect of IL-4 was blocked by anti-IL-4 antibody but not by control antibody. Moreover, IFN-alpha and IFN-gamma, but not GM-CSF, overcame the reducing effect of IL-4. PTH also inhibited IgG, IgM, and IgA production by tonsillar B cells stimulated with Staphylococcus aureus Cowan strain I (SAC) and IL-6 without affecting proliferation. This inhibition was blocked by anti-IL-4 antibody but not by control antibody. These results indicate that, in addition to its regulatory effect on calcium metabolism, PTH also acts as an immunoregulatory factor, and that it interacts with the cytokine, IL-4.
 ...
PMID:Parathyroid hormone inhibits immunoglobulin production without affecting cell growth in human B cells. 145 31

Production of interleukin 1 beta (IL-1 beta), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-alpha), interleukin 2 (IL-2), interferon gamma (IFN-gamma) and granulocyte-macrophage colony-stimulating factor (GM-CSF) after stimulation by lipopolysaccharide (LPS) and phytohemagglutinin (PHA) was studied in 1/10 diluted whole blood (WB) culture and in peripheral blood mononuclear cell (PBMC) culture. Cytokines IL-1 beta, TNF-alpha and IL-6 are preferentially stimulated by LPS whereas IL-2, IFN-gamma and GM-CSF are stimulated by PHA. Combination of 5 micrograms/ml PHA and 25 micrograms/ml LPS gave the most reliable production of the six cytokines studied. IL-1 beta, TNF-alpha and IL-6 represent a homogeneous group of early-produced cytokines positively correlated among themselves and with the number of monocytes in the culture (LeuM3). Furthermore, IL-1 beta was negatively correlated with the number of T8 lymphocytes. IL-2, IFN-gamma and GM-CSF represent a group of late-produced cytokines. Kinetics and production levels of IL-6 and GM-CSF are similar in WB and PBMC cultures. In contrast, production levels of TNF-alpha and IFN-gamma are higher in WB than in PBMC whereas production levels of IL-6 and IL-2 are lower in WB than in PBMC. Individual variation in responses to PHA + LPS was always higher in PBMC cultures than in WB cultures. The capacity of cytokine production in relation to the number of mononuclear cells is higher in WB, or in PBMC having the same mononuclear cell concentration as WB, than in conventional cultures of concentrated PBMC (10(6)/ml). Because it mimics the natural environment, diluted WB culture may be the most appropriate milieu in which to study cytokine production in vitro.
 ...
PMID:Direct stimulation of cytokines (IL-1 beta, TNF-alpha, IL-6, IL-2, IFN-gamma and GM-CSF) in whole blood. I. Comparison with isolated PBMC stimulation. 149 59

Recombinant 15N-labeled human interleukin 2 (IL-2) has been studied by 2D and 3D NMR using uniformly 15N-labeled protein. Assignment of the backbone resonances has enabled the secondary structure of the protein to be defined. The secondary structure was found to consist of four alpha-helical regions and a short section of antiparallel beta-sheet. This structure is more similar to recent published structures of interleukin 4 and granulocyte-macrophage colony-stimulating factor than to a structure of IL-2 previously obtained from low-resolution X-ray diffraction data.
 ...
PMID:Secondary structure of human interleukin 2 from 3D heteronuclear NMR experiments. 151 Sep 60

The cytokines tumor necrosis factor alpha (TNF alpha), granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte colony-stimulating factor (G-CSF), and interleukin 1 (IL 1) all caused an upregulation of C3b receptors (CR1) on neutrophils that ranged from around 76% (G-CSF and IL 1) to 93% (TNF alpha and GM-CSF) of the upregulation obtained by pretreatment of the neutrophils with the chemotactic peptide FMLP. However, only TNF alpha and G-CSF caused a significant increase in phagocytosis of opsonized microspheres. Platelet derived growth factor, interleukin 2, and transforming growth factor beta had no effect on either of these parameters. The mediators platelet activating factor (PAF) and leukotriene B4 (LTB4) both caused a large upregulation of CR1 (93% and 80%, respectively, of the FMLP-mediated value); however, only PAF caused a significant enhancement of phagocytosis by the neutrophils. Prostaglandin E2 and thromboxane B2 had no effect on these parameters. Considerable individual variation was observed among some of the untreated and mediator-treated neutrophil preparations regarding CR1 expression and phagocytosis. The upregulation of CR1 and associated increase in phagocytic capacity of neutrophils caused by certain cytokines and other mediators may be important in host defense. Also the lack of enhancement of phagocytosis accompanying an upregulation of CR1 is unusual and may have important implications regarding the cellular mechanisms of phagocytosis by neutrophils.
 ...
PMID:The effects of cytokines, platelet activating factor, and arachidonate metabolites on C3b receptor (CR1, CD35) expression and phagocytosis by neutrophils. 171 88

Granulocyte-macrophage colony-stimulating factor (GM-CSF) was added to a culture of human peripheral blood mononuclear cells in the presence of interleukin 2 (IL-2) in vitro to elucidate its effect on the induction of lymphokine-activated killer (LAK) cells. Viable cell counts of cultured cells and their cytotoxic effects against natural killer (NK) cell-resistant Daudi cells and NK cell-sensitive K562 cells were measured using the trypan blue dye exclusion test and a 51Cr release assay from the tumor cells, respectively. Although GM-CSF alone did not influence either the cytotoxicities or the surface phenotypes of the cultured cells, the viable cell counts were significantly increased by the addition of GM-CSF in the presence of IL-2 (P less than 0.01). These findings indicate that the addition of GM-CSF in the presence of IL-2 during the induction of LAK cells is useful for obtaining a larger number of effector cells which possess substantial cytotoxic activity.
 ...
PMID:The effects of recombinant human granulocyte-macrophage colony-stimulating factor on the induction of lymphokine-activated killer cells in vitro. 178 73

Cutaneous eruptions displaying perivascular inflammatory cell infiltrates histologically may develop with the intravenous administration of cytokines. Similar findings are seen spontaneously in some patients on recovery of peripheral blood lymphocytes after profound marrow aplasia. To investigate the production of a cutaneous perivascular infiltrate further, the ability of several cytokines to induce a perivascular lymphocytic infiltrate was studied in vitro using a skin explant model. A skin biopsy specimen obtained at the time of peripheral blood lymphocyte recovery after chemotherapy-induced marrow aplasia (n = 10) was divided and incubated for 3 days with and without a series of cytokines plus various peripheral blood mononuclear cell populations. Skin incubated with interleukin 2 and granulocyte-macrophage colony-stimulating factor induced a perivascular lymphocytic infiltrate, while control samples did not. Immunophenotypic analysis revealed that the lymphocytes were predominantly CD3+/CD4+. An infiltrate was not observed when skin was incubated with cytokines alone, without the addition of simultaneously isolated peripheral lymphocytes. A perivascular pattern was not observed with the addition of interferon gamma. Only interferon gamma induced keratinocyte intercellular adhesion molecule 1 expression in experimental tissue. Certain cytokines that affect a range of cell types are capable of inducing a common cutaneous histologic pattern, the perivascular lymphocytic infiltrate.
 ...
PMID:Interleukin 2 and granulocyte-macrophage colony-stimulating factor induce a perivascular lymphocytic infiltrate in a skin explant model. 184 77

We have previously shown that the interaction of thymocytes with thymic accessory cells (macrophages and/or interdigitating cells) is one of the factors required for thymocyte activation. Precursors of both thymic accessory cells and thymocytes are included in the CD4- CD8- Mac-1- Ia- subpopulation, and their respective maturation and/or activation may be modulated by granulocyte-macrophage colony-stimulating factor, interleukin 1 and interleukin 2. When CD4- CD8- thymic cells are activated with granulocyte-macrophage colony-stimulating factor plus interleukin 2, both macrophages and interdigitating-like cells are present, as shown by electron microscopy. When activated with interleukin 1 plus interleukin 2, the interdigitating-like cell is the only accessory cell present. In both culture conditions, large clusters are formed between interdigitating cells and lymphoid cells. These results have led us to propose two-step signals for thymocyte proliferation: first, the maturation of macrophages under granulocyte-macrophage colony-stimulating factor control and the production of interleukin 1, and secondly, the maturation of interdigitating cells under interleukin 1 control, their clustering with thymocytes which are then activated.
 ...
PMID:Effect of cytokines on thymic hematopoietic precursors. Phenotypic and electron-microscopic study. 187 49

We have shown that incubation of bone marrow (BM) with interleukin 2 (IL-2) generates activated bone marrow cells (ABM) with potent tumoricidal activity in vitro and in vivo. The present study was carried out to define the interaction of other cytokines with IL-2 in generation of ABM. Our data show that interleukin 1 (IL-1), interferon (IFN)- both gamma and alpha, and tumor necrosis factor (TNF-alpha) significantly increased the cytolytic potential of ABM. Interleukin 3, interleukin 4, transforming growth factor-beta and adherent cells were reduced, while granulocyte-macrophage colony-stimulating factor had no influence on the generation of cytolytic activity. IL-1 was enhanced while TNF-alpha depressed the BM progenitor cell activity in vitro. The IL-2-induced purging ability of BM contaminated with leukemic cells was increased by IL-1, TNF-alpha and IFN-gamma. This study shows that biomodulation of BM with combination of cytokines in vitro can be useful in purging a large leukemic burden.
 ...
PMID:Interaction of various cytokines with interleukin 2 in the generation of killer cells from human bone marrow: application in purging of leukemia. 192 58

Murine T helper type 2 clones were stimulated with immobilized anti-CD3 antibody or with recombinant lymphokines to compare the expression of T-cell activation genes induced by these stimuli. Immobilized anti-CD3 antibody, recombinant interleukin 2 (IL-2), and recombinant interleukin 4 (IL-4) all induced proliferation of the T helper type 2 clones 10-5-17 and D10. Proliferation of these clones induced by anti-CD3 antibody was completely inhibited by cyclosporine A, whereas cyclosporine A had little effect on proliferation induced by recombinant IL-2 or recombinant IL-4. Both immobilized anti-CD3 antibody, and recombinant IL-2 induced the expression of the protooncogenes c-myc and c-myb. Immobilized anti-CD3 antibody also induced expression of the lymphokine genes IL-4, interleukin 5 (IL-5), and granulocyte-macrophage colony-stimulating factor. In contrast, recombinant IL-2 induced IL-5 mRNA expression but did not induce detectable expression of IL-4 or granulocyte-macrophage colony-stimulating factor mRNA. Likewise, recombinant IL-4 induced expression of IL-5 but not IL-4 mRNA. Thus, the IL-4 and IL-5 genes appear to be differentially regulated after stimulation with recombinant lymphokines. Effects of cyclosporine A and the protein synthesis inhibitors cycloheximide and anisomycin on IL-4 and IL-5 gene expression suggest that these genes are activated by different pathways after anti-CD3 stimulation. Cyclosporine A completely inhibited anti-CD3-induced expression of IL-4 mRNA but not of IL-5 mRNA, and protein-synthesis inhibitors completely inhibited induction of IL-5 mRNA but not of IL-4 mRNA. Together, our data show that T-cell receptor-mediated and lymphokine receptor-mediated signals induce different patterns of lymphokine gene expression and provide strong evidence that the IL-4 and IL-5 genes are differently regulated.
 ...
PMID:Differential regulation of interleukin 4 and interleukin 5 gene expression: a comparison of T-cell gene induction by anti-CD3 antibody or by exogenous lymphokines. 214 29


1 2 3 4 5 6 Next >>