Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:BIOD00035 (CSF)
 30,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

New experimental findings on the mutual regulation of growth, differentiation and function of human blood cells by growth factors offer the opportunity to use these factors in the treatment of haematological diseases. The hitherto known growth factors are divided into four basic groups: 1. haematopoietic growth factors proper [multi-CSF (IL-3), GM-CSF, G-CSF, M-CSF, erythropoietin, lymphopoietin (IL-7) and megakaryopoietin (IL-11)], 2. cytokines (IL-1 to IL-11, TFN)., 3. other growth factors (PDGF, FGF, MGF) and 4. so-called negative regulators of haematopoiesis (IFN, MIP, TGF beta and IL-10), some of which support the differentiation of stem cells. Before growth factors can be routinely used in clinical work, it is essential to acquire closer knowledge of their interrelations, the activity of their receptors and natural or acquired inhibitors in vivo.
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PMID:[Growth factors in hematology]. 136 11

Cytokines may play an important role in the regulation of host defense against local bacterial infections. We have evaluated the local production of cytokines in a BALB/c mouse model of Escherichia coli pyelonephritis. Kidneys, draining lymph nodes, and spleens, were harvested at specific time intervals after bladder inoculation with E. coli corresponding to the stages of renal infection, infiltration, and bacterial clearance seen in this model. The presence of messenger RNA for specific cytokines (interleukins 1 through 6, chemotactic factors, granulocyte and granulocyte macrophage-colony stimulating factor (GM-CSF), tumor necrosis factor (TNF alpha) and beta, IFN gamma, transforming growth factor (TGF beta), and cytokine synthesis inhibitory factor (CSIF)/IL-10) was determined by polymerase chain reaction (PCR) amplification of reverse transcribed RNA. We have demonstrated mRNA encoding IL-1, IL-6, G-CSF, GM-CSF, TNF alpha, H400 (a protein homologous to a family of chemotactic factors and identical to MIP-1 beta), and CSIF/IL-10 in the kidney at 12 h and 1, 2, and 3 d after bacterial challenge. No signal was seen in normal animals or in mice after 5 d. This pattern of cytokine expression was observed only in renal tissues suggesting a localized response. IL-6 was present in the urine at 4 h with rapid resolution to baseline levels by 24 to 48 h. In contrast, IL-6 was not usually detectable in the serum. TNF alpha was not detectable in the serum or urine during the course of the infection. By immunohistochemical staining of kidney sections we have shown that IL-6 is produced predominantly by mesangial cells rather than by the inflammatory infiltrate. This study provides additional evidence utilizing novel techniques that specific cytokines are produced locally in response to bacterial infections. The time course of production demonstrated in this model supports the important role of cytokines in natural host resistance to local infection.
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PMID:Local cytokine production in a murine model of Escherichia coli pyelonephritis. 154 64

Macrophage inflammatory protein 1 (MIP 1), initially purified from the conditioned medium of endotoxin-stimulated macrophages, is a low m.w. heparin-binding protein doublet comprising two peptides, MIP 1 alpha and MIP 1 beta. Although native doublet MIP 1 has previously been shown to exert pyrogenic, mitogenic, and proinflammatory effects on other cell types, its actions on its cell of origin, the macrophage, have not been well catalogued. Our study reports several aspects of macrophage function that are modulated by MIP 1. MIP 1 was not directly cytotoxic for WEHI tumor cells, but MIP 1-treated macrophage exhibited enhanced antibody-independent macrophage cytotoxicity for tumor targets. MIP 1 treatment stimulated proliferation of mature tissue macrophages, and this effect was enhanced upon costimulations with either CSF-1 or granulocyte-macrophage-CSF. Thioglycollate-elicited peritoneal exudate macrophages incubated with native doublet MIP 1-secreted bioactive TNF and IL-6, as well as immunoreactive IL-1 alpha, and these effects were enhanced significantly when the cells were costimulated with IFN-gamma. Purified preparations of the recombinantly derived MIP 1 alpha peptide alone stimulated the secretion of TNF, IL-1 alpha, and IL-6 by peritoneal macrophages, but MIP 1 beta did not. In fact, as little as eightfold excess MIP 1 beta blocked TNF-induction by MIP 1 alpha to a significant degree. By contrast to these apparent "macrophage activating" properties of MIP 1, the cytokine failed to trigger the macrophage oxidative burst, or to up-regulate the expression of Ia on the macrophage surface. Taken together, these data reveal that MIP 1 peptides act as autocrine modulators of their cells of origin, and raise the possibility that MIP 1 peptides may play a role in modulating macrophage responses to inflammatory stimuli in vivo.
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PMID:Macrophage inflammatory protein 1 modulates macrophage function. 157 67

We have examined the effects of 10 different growth factors either alone or in combination on colony-forming unit-spleen (CFU-S) and repopulating stem cell survival in vitro. Either interleukin-3 (IL-3), granulocyte-colony-stimulating factor (G-CSF), or IL-4 alone support CFU-S in vitro. The effects of IL-3 or G-CSF could be neutralized by adding antibodies against IL-3 or G-CSF, respectively. However, the effects of IL-4 could be neutralized with antibodies to IL-4 as well as with antibodies to IL-3 and G-CSF. The combinations of IL-3 and IL-6, IL-3 and G-CSF, IL-3 and IL-1 alpha, IL-3 and granulocyte-macrophage CSF (GM-CSF), and IL-4 and IL-6 acted synergistically to increase CFU-S number. Addition of macrophage inflammatory protein-1 alpha (MIP-1 alpha) to IL-3 and IL-6 inhibited the increase in CFU-S number. Repopulating stem cell function was measured in a competitive repopulation assay. Either IL-3 or IL-4 alone could preserve stem cell function in vitro. The combinations of IL-3 and IL-6, and IL-3 and G-CSF increased stem cell function approximately twofold. The combinations of IL-3 + G-CSF + IL-6, and IL-4 and IL-6 (both of which increased CFU-S number fivefold to 10-fold) decreased stem cell function approximately fourfold. These results demonstrate that certain combinations of growth factors can increase CFU-S number at the expense of stem cell function.
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PMID:Effects of hematopoietic growth factors on the survival of primitive stem cells in liquid suspension culture. 171 28

Granulocyte/macrophage colony-stimulating factor (GM-CSF) specifically induces the growth of myeloid progenitors and their maturation into neutrophils and macrophages. We have identified a series of previously uncharacterized hematopoietic-specific mRNAs that are expressed in myelopoietic mouse bone marrow cultures stimulated by GM-CSF. One of these messages, C10, encodes a new member of the family of cytokine-like genes related to macrophage inflammatory protein-1 (MIP-1). Members of this family are all induced by one or more stimuli related to inflammation, wound repair, or immune response. In contrast, C10 mRNA showed little or no accumulation in response to such activating agents and was greatly reduced on activation of a T-cell line. On the other hand, C10 mRNA, unlike MIP-1, was acutely stimulated during the first day of bone marrow culture in GM-CSF, and it was also strongly elevated during the induction of neutrophilic differentiation of 32D cl3 cells by granulocyte colony-stimulating factor. The implications of this unusual expression pattern are discussed.
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PMID:Novel expression pattern of a new member of the MIP-1 family of cytokine-like genes. 183 65

Two recently identified and purified murine macrophage inflammatory proteins MIP-1 and MIP-2 were tested in vitro both alone, and in combination with purified recombinant (r) murine (mu) GM-CSF, natural (n)muCSF-1, or rhuman (hu)G-CSF, for effects on mouse marrow CFU-GM, in combination with erythropoietin for effects on mouse marrow BFU-E, and in combination with rhuGM-CSF or rhuG-CSF for effects on human marrow CFU-GM. MIP-1 and MIP-2 did not stimulate, but did enhance by up to threefold, colony formation of mouse CFU-GM co-stimulated by rmuGM-CSF and nmuCSF-1, but not by rhuG-CSF, in the absence or presence of serum. MIP-1 and MIP-2 were maximally active at concentrations greater than or equal to 100 ng/ml and the actions appeared to be initiated during the DNA synthetic portion of the cell cycle. Neither MIP-1 nor MIP-2 at up to 1 microgram/ml had any effect on mouse BFU-E, in the absence or presence of erythropoietin. Both MIP-1 and MIP-2 had direct acting effects on purified mouse CFU-GM. The cloning efficiency of 200 purified cells plated with 50 U muCSF-1 was 82% with and 43% without MIP; the cloning efficiency with 50 U rmuGM-CSF was 65% with and 35% without MIP. MIP effects were not mimicked by bacterial LPS, rhuIL-1 alpha, rhuIL-6, or rmuIL-4, and were neutralized by their respective specific antibodies. MIP-1 and MIP-2 also enhanced endogenously stimulated and rhuGM-CSF-, but not rhuG-CSF-, stimulated colony formation by human marrow CFU-GM. These results demonstrate a new role for MIP-1 and MIP-2 in vitro as myelopoietic enhancing activities for CFU-GM.
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PMID:Myelopoietic enhancing effects of murine macrophage inflammatory proteins 1 and 2 on colony formation in vitro by murine and human bone marrow granulocyte/macrophage progenitor cells. 247 52

Mast cells are critical effectors in many IgE-dependent responses, and the numbers and phenotype of certain mast cell populations can be influenced, through IL-3 and IL-4, by the same T cells that regulate IgE production. However, IgE can interact with cells other than mast cells, and different mast cell populations express significant variation in multiple important aspects of their phenotype, including mediator content and responses to cytokines and stimuli of activation. As a result it may be difficult to define the unique contributions of mast cells to IgE-dependent reactions. One approach for analysing the roles of various mast cell populations in individual biological responses is to attempt to elicit these reactions in mice in which the presence or absence of specific mast cell populations can be regulated experimentally. We have used genetically mast cell-deficient and mast cell-reconstituted mice to demonstrate that mast cells provide essential effector function in certain IgE-dependent responses involving the skin, stomach or lungs but are not necessary for the pulmonary alterations and death associated with active anaphylaxis. Similar approaches can be used to investigate the biological significance of the production, by mast cells stimulated with IgE and specific antigen, of cytokines similar or identical to IL-1, IL-3, IL-4, IL-5, IL-6, TNF-alpha/cachectin, IFN-gamma, GM-CSF, JE, MIP-1 alpha, MIP-1 beta and TCA3.
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PMID:Mast cells: immunologically specific effectors and potential sources of multiple cytokines during IgE-dependent responses. 251 50

As an attempt to elucidate the pathogenesis of human immunodeficiency virus type 1 (HIV-1)-related cytopenia, the effects of infection of long-term primary bone marrow culture (LTBMC)-derived adherent cells on hematopoiesis were investigated. Productive infection could then be established only when using monocytotropic strains HIV-1Ba-L, HIV-1Ada, and HIV-1JR-FL but not with lymphocytotropic strain HIV-1LAI. Culture supernatants were tested for major cytokines involved in the regulation of hematopoiesis: neither IL-3 nor GM-CSF were detectable in the infected or noninfected cultures; in contrast, TGF-beta, TNF-alpha, MIP-1 alpha, Steel Factor, and IL-6 were detected at all times in established LTBMCs, but their levels were not consistently altered by virus replication. In vitro functional analysis by colony and long-term culture assays showed that HIV-1 infection failed to alter either the kinetics or the number of hematopoietic progenitors produced by the stromal layers; it did not interfere with the clonogenicity of exogeneous CD34+ cells in semisolid assays, and no difference was observed relative to the controls when HIV-1-infected stromal layers were tested for their ability to sustain long-term hematopoiesis. These results show that productive and sustained virus replication in the macrophage component of LTBMCs does not significantly alter the profile of major cytokines involved in regulating hematopoiesis, nor is it sufficient by itself for altering in vitro hematopoiesis under the baseline conditions used.
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PMID:In vitro infection of bone marrow-adherent cells by human immunodeficiency virus type 1 (HIV-1) does not alter their ability to support hematopoiesis. 748 69

The myelosuppressive effects of human chemokines were evaluated in vitro on normal myeloid progenitors obtained from bone marrow and cord blood, on bone marrow progenitors from patients with acute or chronic leukemia, on proliferation of human factor-dependent cell line M07e, and in vivo on myelopoiesis in mice. Preincubation of human MIP-1 alpha, MIP-2 alpha, interleukin (IL)-8, platelet factor (PF) 4, monocyte chemotactic and activating factor (MCAF), and interferon-inducible protein-10 (IP-10) in an acetonitrile (ACN) solution significantly enhanced the specific activity of these chemokines for in vitro suppression of granulocyte-macrophage (CFU-GM), erythroid (BFU-E), and multipotential (CFU-GEMM) progenitor cells stimulated to proliferate with a colony stimulating factor plus steel factor (SLF). Combinations of any two of these ACN-treated chemokines synergized to suppress colony formation of CFU-GM, BFU-E, and CFU-GEMM at chemokine concentrations below that at which combinations of non-ACN treated chemokines are active. Cord blood progenitors, as previously reported, were in a slow or noncycling state and nonresponsive to inhibition by chemokines. However, after suspension culture with GM-CSF, IL-3, and SLF, they were placed into rapid cell cycle and were responsive to inhibition by ACN-treated chemokines. Low doses of these ACN-pretreated chemokines were active in vivo in suppressing absolute numbers and cycling status of femoral marrow CFU-GM, BFU-E, and CFU-GEMM in C3H/HeJ mice. Other chemokines, alone and in combination, including MIP-1 beta, MIP-2 beta, GRO-alpha NAP-2, and RANTES, were inactive in vitro and in vivo whether or not they were pretreated with ACN. While heterogeneity in responsiveness of CFU-GM from different patients with leukemia to suppression by ACN-treated chemokines was apparent, if the patients had CFU-GM responsive to one of the active chemokines these cells were responsive to the other active chemokines; if patient CFU-GM were not responsive to one of the chemokines, they were not responsive to the other active chemokines. M07e colony-forming cells were responsive to the growth-inhibiting effects of the active ACN-treated chemokines, alone and in combination, but these effects were rapidly reversible and sustained only by multiple daily additions of chemokines. These results should be of value in considering these chemokines for potential clinical use and for assessment of their mechanisms of action, alone and in combination.
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PMID:Human chemokines: enhancement of specific activity and effects in vitro on normal and leukemic progenitors and a factor-dependent cell line and in vivo in mice. 749 26

Human neutrophils at inflammatory sites may be an important source of the chemotactic cytokines macrophage inflammatory protein 1 alpha (M1P-1 alpha; a C-C chemokine) and interleukin 8 (IL-8; a C-X-C chemokine). In this study, we show that the inflammatory microcrystals monosodium urate monohydrate (MSU) and calcium pyrophosphate dihydrate (CPPD), the major mediators of gout and pseudogout, differentially regulate the production of these two chemokines by human neutrophils. Both MSU and CPPD increased the secretion of IL-8 by neutrophils in a dose- and time-dependent manner, but had no effect on that of MIP-1 alpha. Since inflammatory cytokines are likely to be present in the synovium during crystal-induced inflammation, we examined the interaction between TNF-alpha and GM-CSF and the crystals. Both TNF-alpha and GM-CSF stimulated IL-8 production; however, only TNF-alpha exerted a significant effect on MIP-1 alpha secretion in neutrophils. IL-8 production induced by TNF-alpha and GM-CSF was synergistically enhanced in the presence of MSU or CPPD, whereas MIP-1 alpha secretion induced by TNF was completely inhibited in the presence of either MSU or CPPD. Interestingly, no interaction between the crystals and the inflammatory cytokines was observed with respect to synthesis of the C-X-C chemokine MGSA in neutrophils. These results suggest that the combination of TNF-alpha and GM-CSF with MSU or CPPD will lead to the production of IL-8 by neutrophils and abolish the release of MIP-1 alpha, an event that will theoretically lead to recruitment of neutrophils but not mononuclear cells. These results are in accordance with the pathological state of gout and pseudogout, where the predominant inflammatory cell is the neutrophil.
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PMID:Inflammatory microcrystals differentially regulate the secretion of macrophage inflammatory protein 1 and interleukin 8 by human neutrophils: a possible mechanism of neutrophil recruitment to sites of inflammation in synovitis. 750 47


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