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)

Proliferation in vitro of the in vivo passaged murine B cell tumor line BCL1 has been used as a standard assay for mouse interleukin-5 (IL-5) for a number of years. We demonstrate that this line will also respond to human IL-5. The response to murine IL-5 is abrogated by transforming growth factor-beta and to a lesser extent by interferon-gamma. This suggests a possible regulatory role for these lymphokines in the proliferation of B cells induced by IL-5. Other purified recombinant lymphokines were also tested for their ability to induce BCL1 proliferation. The lymphokines IL-1, IL-2, IL-3, and IL-6 had no effect on the growth of BCL1. In contrast, IL-4 and more surprisingly granulocyte-macrophage colony-stimulating factor (GM-CSF) also induced proliferation of this cell. These effects could be inhibited by specific antibodies directed against the respective lymphokines. These data suggest that GM-CSF, as well as IL-4 and IL-5, may be yet another regulator of neoplastic and possibly even normal B-cell growth and differentiation.
 ...
PMID:The BCL1 B lymphoma responds to IL-4, IL-5, and GM-CSF. 267 47

In order to maintain adequate circulating numbers of blood cells, the bone marrow must produce billions of cells each day and must be able to rapidly increase production by 10-20-fold in response to infection and hemorrhage. The existence of circulating factors that regulate this process has been suspected for over 100 years. Recently, the genes encoding these growth factors were cloned and their functions are now identified. Interleukin-3 (IL-3) acts on the most primitive hematopoietic stem cell, driving this self-renewing cell to produce progeny of all hematopoietic lineages. Granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulates the granulocyte-macrophage progenitor cell, as well as cells committed to the erythroid lineage, to differentiate. G-CSF and M-CSF stimulate the most differentiated myeloid progenitors to produce granulocytes and monocytes/macrophages, respectively. Erythropoietin stimulates the differentiation of late erythroid progenitors. In the lymphoid progenitor lineage, IL-2 stimulates T cell differentiation; IL-4 and IL-6 stimulate differentiation of B cells. The colony-stimulating factors also enhance function and cause activation of the mature cells whose production they induce. In clinical trials, these hormones have successfully ameliorated anemia in renal failure, chronic disease, and in prematurity. They have improved pancytopenias in aplastic anemia, myelodysplastic syndromes, and congenital cytopenias, and they have hastened recovery from chemotherapy and bone marrow transplantation.
 ...
PMID:Hematopoietic hormones: from cloning to clinic. 267 59

We have examined the effects of four well-characterized cytokines with T lymphocyte-stimulatory activity, i.e., interleukin (IL)-2, IL-3, IL-4, and granulocyte-macrophage colony-stimulating factor (GM-CSF) on [3H]-thymidine incorporation in peripheral blood mononuclear cells (PBMs) obtained from patients with psoriasis. Under the influence of these cytokines, the incorporation of [3H]-thymidine into the PBMs was not different between psoriatic patients and healthy controls either in culture supplemented with pooled AB serum or with autologous serum. However, a potent immunopotentiator OK-432, which is a lyophilized preparation of penicillin-treated low virulence Su-strain of Streptococcus pyogenes group A3, induced significantly less incorporation of [3H]-thymidine into the PBMs from psoriatic patients than those from healthy controls [in both the culture supplemented with pooled AB serum (p less than 0.01) and that with autologous serum (p less than 0.01)]. This reduction in thymidine uptake was closely related to the disease activity as well as to the extent of skin lesions of the psoriatic patients. The defective immune response of PBMs from psoriatic patients to OK-432 probably reflects an abnormality at the level of interaction between monocytes and T cells or at the subsequent production and release of cytokines by them.
 ...
PMID:Proliferative responses of peripheral blood mononuclear cells from psoriatic patients to T lymphocyte-stimulating cytokines (IL-2, IL-3, IL-4, and granulocyte-macrophage colony-stimulating factor) and OK-432. 267 7

The effects of recombinant hemopoietic factors on the clonal growth of human megakaryocyte progenitors were explored using serum-free cultures of nonadherent and T-cell-depleted marrow cells. Recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF) supported megakaryocyte colony formation in a dose-dependent manner, the activity being lower than that of recombinant interleukin 3 (rIL-3). Recombinant IL-3 and rGM-CSF acted synergistically on megakaryocyte colony formation when rGM-CSF was added to cultures containing suboptimal concentrations of rIL-3. However, the number and size of colonies did not increase with rGM-CSF when cultures were plated with an optimal dose of rIL-3. Recombinant erythropoietin (rEpo) by itself did not stimulate the growth of megakaryocyte progenitors. Recombinant Epo did, however, produce a significant increase in the number and size of megakaryocyte colonies in the presence of rIL-3 or rGM-CSF. Other factors, including recombinant granulocyte colony-stimulating factor, recombinant interleukin 1 alpha, recombinant interleukin 4, and recombinant interleukin 6 showed no capacity to generate or enhance megakaryocyte colony formation when added to cultures alone or in combination with varying concentrations of rIL-3. These results show that rIL-3, rGM-CSF, and rEpo affect human megakaryocytopoiesis by themselves or by interacting with each other.
 ...
PMID:Effect of recombinant hemopoietic growth factors on human megakaryocyte colony formation in serum-free cultures. 268 May 66

The effects of human recombinant interleukin 6 (rIL-6) on in vitro human megakaryocytopoiesis were studied utilizing a serum-depleted culture system. Recombinant IL-6 increased both the number of megakaryocyte (MK) colonies formed and the number of cells comprising individual MK colonies cloned from normal low-density bone marrow (LDBM) cells. This stimulation of MK colony number and size was significantly less than that observed following the addition of recombinant interleukin 3 (rIL-3) or granulocyte-macrophage colony-stimulating factor (rGM-CSF). The addition of either rIL-3 or rGM-CSF, but not rIL-6 promoted MK colony formation by nonadherent, low-density, T-cell-depleted (NALDT-) marrow cells. Recombinant interleukin 1 alpha (rIL-1 alpha) and interleukin 4 (rIL-4) failed either to promote LDBM MK colony formation when added alone or to significantly increase rIL-6-promoted MK colony formation. MK colony formation promoted by optimal doses of rIL-6 was, in fact, significantly inhibited by rIL-1 alpha at all concentrations tested. Addition of either recombinant erythropoietin (rEpo) or purified thrombocytopoiesis-stimulating factor (TSF) to assays containing rIL-6 also resulted in significant inhibition of MK colony formation. The effect of suboptimal concentrations of rIL-6 on MK colony formation was additive to that of rIL-3 but not rGM-CSF. The addition of transforming growth factor beta (TGF-beta) resulted in a 58% reduction of rIL-6-promoted MK colony formation by LDBM. These data suggest that rIL-6 can promote in vitro megakaryocytopoiesis and that this effect can be either augmented or inhibited by the addition of several other cytokines. Recombinant IL-6, however, might affect the MK colony-forming unit (CFU-MK) by acting through bone marrow accessory cells or requiring the presence of as yet unidentified additional cytokines.
 ...
PMID:Effect of interleukin 6 on in vitro human megakaryocytopoiesis: its interaction with other cytokines. 268 May 67

Because inflammatory processes in renal glomeruli may involve monocyte-macrophages (MPs) and T-lymphocytes, we have investigated whether products of glomerular mesangial cells (MCs) can stimulate the proliferative activity of these effector cells. We found that cultured rat MCs (subcultures 2-15), maintained under serum-free conditions, secrete a soluble factor into the supernate [MC-conditioned medium (CM)], which supports growth of the T-helper cell-derived line HT-2. Moreover, MC-CM increased [3H]thymidine incorporation by thioglycollate-elicited peritoneal MPs but did not induce growth of the interleukin 2 (IL-2)- or interleukin 4 (IL-4)-dependent cell line CTLL-2. Further functional, serological, and biochemical analysis of MC-CM revealed that rat MCs secrete a cytokine that, by all of the techniques used, is indistinguishable from granulocyte-macrophage colony-stimulating factor (GM-CSF). Both northern blot and in situ hybridization with a specific cDNA probe for murine GM-CSF showed that MCs express GM-CSF mRNA transcripts. The present findings indicate that cultured rat MCs produce GM-CSF. Release of GM-CSF by MCs in vivo may play a role in the interaction of MCs with MPs, T-cells, and neutrophils in glomerular disease.
 ...
PMID:Rat mesangial cells produce granulocyte-macrophage colony-stimulating factor. 269 Jun 41

Osteoblasts play a central role in the regulation of bone remodeling. Not only are they responsible for the formation of new bone, but they also regulate bone resorption. These cells also exert regulatory influences outside the bone in that they are able to regulate hematopoiesis. However, obtaining pure populations of osteoblasts devoid of contaminating cell types remains problematic. One approach to this problem is the use of cloned osteoblastic cell lines. To this end we have used MC3T3-E1, a cloned murine osteoblast cell line of C57BL/6 origin. We report that MC3T3-E1 cells respond to lipopolysaccharide (LPS) and, to a lesser extent, parathyroid hormone (PTH) by the secretion of granulocyte-macrophage colony-stimulating factor (GM-CSF). However, 1,25-(OH)2D3, a potent activator of osteoblasts, fails to induce these cells to secrete GM-CSF. These results suggest that MC3T3-E1 cells respond to osteotropic agents in a hierarchical fashion. Secretion of GM-CSF is not constitutive but rather requires active induction of the cells. MC3T3 cells fail to secrete detectable levels of interleukin-2 (IL-2), IL-3, or IL-4, regardless of whether or not the cells are activated. The data indicate that MC3T3-E1 cells secrete cytokines in response to osteotropic agents in a way similar to that of normal primary osteoblasts. Therefore, MC3T3-E1 cells may serve as a good in vitro model for primary osteoblasts.
 ...
PMID:Osteotropic agents induce the differential secretion of granulocyte-macrophage colony-stimulating factor by the osteoblast cell line MC3T3-E1. 269 6

The histamine-producing cell-stimulating factor (HCSF) was first described as a lymphokine which is produced during secondary mixed leukocyte culture and which induces increased histamine synthesis by murine hematopoietic cells. It has been shown that it is different from interleukin 3 (IL 3), despite the fact that pure IL 3 expresses HCSF activity. Our results provide evidence that this factor (constitutively produced by the P388 D1 cell line) is identical with granulocyte-macrophage colony-stimulating factor (GM-CSF) i.e.: (a) physiochemical properties of HCSF and GM-CSF, such as molecular weight, isoelectric charge, hydrophobicity and behavior during affinity chromatography, are indistinguishable and both activities coelute during all biochemical purification procedures; (b) increased bone marrow cell histamine synthesis induced by P388 D1-derived HCSF is inhibited by anti-GM-CSF antiserum; (c) the GM-CSF cDNA probe hybridizes with a poly(A)+RNA from P388 D1 cells while no hybridizing signal was obtained with poly(A)+RNA from WEHI-3 and from P815 cells. On the other hand, the IL 3 cDNA probe hybridizes with a 1.0-kb poly(A)+RNA from WEHI-3 but not with those from P388 D1 and P815. Moreover, well known sources of GM-CSF, such as lung conditioned medium and semi-purified GM-CSF from phytohemagglutinin-induced supernatant of the murine T lymphoma LBRM-33-5 A4 (preparation devoid of IL 3), as well as recombinant murine GM-CSF, induce increased histamine synthesis by hematopoietic cells. All these results demonstrate that, in our culture conditions, the P388 D1 cell line spontaneously produces GM-CSF which is responsible for the P388 D1-induced HCS activity. Consequently, the latter is a property shared by the two distinct hematopoietic growth factors acting on the less committed cells, i.e. IL 3 and GM-CSF, whereas M-CSF or G-CSF are unable to induce histamine production. Interestingly, IL-4 which is known to support established mast cell line proliferation cannot induce HCS activity. In addition, none of the other cytokines tested, such as IL 1, IL 2, interferons or tumor necrosis factor can express HCS activity. This expression seems to be a specific property of IL 3 and GM-CSF.
 ...
PMID:Histamine-producing cell-stimulating activity. A biological activity shared by interleukin 3 and granulocyte-macrophage colony-stimulating factor. 288 59

Lymphokine activities in conditioned medium from activated helper T cell lines are most commonly defined by the proliferation of "specific" lymphokine-dependent cell lines. Various sublines of IL 2-dependent (and ostensibly specific) HT-2 and CTLL cells have now been shown to proliferate in response to BSF-1/IL 4 as well. After activation with antigen or mitogen, D10.G4.1, an antigen-specific cloned T helper cell that has recently been shown to produce IL 4 but not IL 2, secretes two distinct cytokines that induce the growth of HT-2 cells. These "T cell growth factors" (TCGF) can be separated by reversed phase high-performance liquid chromatography (RP-HPLC). The TCGF activity of one of these factors can be blocked by 11B11, an antibody specific for IL 4. The second TCGF activity is not affected by 11B11 or by antibodies specific for IL 2. This TCGF activity can be neutralized by a goat polyclonal antibody to granulocyte-macrophage colony-stimulating factor (GM-CSF), and has a RP-HPLC elution profile identical to that of recombinant GM-CSF. Recombinant GM-CSF induces both proliferation and long-term growth of HT-2 but not CTLL cells, and this activity can be neutralized by the same antibody to GM-CSF. GM-CSF is best known as a factor that induces the maturation and growth of granulocytes and macrophages from bone marrow-derived hematopoietic precursor cells. The ability of GM-CSF to induce the growth of certain T cell lines indicates that this molecule may play a role in T cell-mediated immune responses, either as an autocrine growth factor or a paracrine stimulus from both lymphoid and nonlymphoid tissues that produce this cytokine.
 ...
PMID:Growth of an interleukin 2/interleukin 4-dependent T cell line induced by granulocyte-macrophage colony-stimulating factor (GM-CSF). 295 4

Supernatants from a subset of helper T cell clones can enhance IgA, IgE, and IgG1 production in cultures of lipopolysaccharide-stimulated, T cell-depleted spleen cells. The lymphokine interleukin (IL)-4 has been shown to cause the IgE and IgG1 enhancement produced by these supernatants. IgA enhancement, however, is mediated by a factor distinct from IL-4, although IL-4 can potentiate the effect of the IgA-enhancing factor. IgA-enhancing factor is also distinct from IL-1, IL-2, IL-3, granulocyte-macrophage colony-stimulating factor, and interferon-gamma and acts directly on B cells. Purified IgA-enhancing factor enhances IgA production three- to sixfold yet causes less than a twofold increase in other isotypes. The IgA enhancing activity is not inhibited by concentrations of interferon-gamma that inhibit IL-4 activities. In the accompanying article, we show that this IgA enhancing activity is a novel property of the lymphokine IL-5.
 ...
PMID:A mouse T cell product that preferentially enhances IgA production. I. Biologic characterization. 296 Jul 39


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>