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

Recombinant interleukin 4 (IL4) down-regulates the expression of CD14 on normal human monocytes, as assessed by flow cytometry, binding assays with radiolabeled anti-CD14 monoclonal antibody (mAb), and immunoprecipitation of 125I-labeled monocytes with anti-CD14 mAb. In parallel, CD23 expression on monocytes was strongly increased by IL4 stimulation, as assessed by both flow cytometry and immunoprecipitation. Down-regulation of surface CD14 was first detectable after 24-36 h of incubation with rIL4, and was almost complete after 4 days of culture. None of the other recombinant lymphokines tested (IL1, IL2, IL3, IL5, IL6, interferon-gamma, tumor necrosis factor alpha and beta, granulocyte-macrophage colony-stimulating factor) decreased CD14 expression. Metabolic labeling studies with [35S]methionine showed that both the membrane-associated and the soluble form of CD14 are decreased by IL4 stimulation. Northern blot analysis showed that incubation of monocytes with IL4 induced a marked decrease in CD14 mRNA. Nuclear run-off assays revealed that the IL4-dependent down-regulation of CD14 resulted from decreased transcription. Thus, IL4 exerts specific and opposite effects on the expression of monocytic antigens.
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PMID:Interleukin 4 down-regulates the expression of CD14 in normal human monocytes. 170 91

An epithelial cell line, IT-45R1, has been established from a thymus of normal Wistar rat and was found to produce growth factor which stimulated the proliferation of bone marrow cells. This growth factor induced the formation of colonies composed of macrophages, granulocytes, or both, in semi-solid medium and stimulated the proliferation of an interleukin 3 (IL3)/granulocyte-macrophage colony-stimulating factor (GM-CSF)-dependent clone. Neither IL3-dependent clone nor IL6-dependent clone responded to IT-45R1 factor. Additionally, IT-45R1 factor acted on both rat and mouse bone marrow cells but not on human bone marrow cells. Molecular weight of IT-45R1 factor was 30 kD and its isoelectric point was 4.5. To determine whether IT-45R1 factor is GM-CSF or not, Northern blot analysis and neutralization with anti-mouse GM-CSF antibody were carried out. IT-45R1 expressed GM-CSF mRNA, but neither M-CSF nor IL6 transcripts. However, antiserum specific for mouse GM-CSF did not neutralize IT-45R1 factor. Taken together, a rat thymic epithelial cell line, IT-45R1, constitutively produces GM-CSF or GM-CSF-like growth factor.
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PMID:Production of granulocyte-macrophage colony-stimulating factor or GM-CSF-like growth factor by rat thymic epithelial cell line. 194 Jun 10

Immunotherapy can be defined as treatment directed at augmenting host immune defence mechanisms. Non-antimicrobial therapies and immunoprophylaxis in bone marrow transplantation (BMT) can be subdivided into three broad categories: passive immunotherapy with intravenous immunoglobulin (IVIG); cytokine therapy; and anti-endotoxin-directed treatments. Most studies using IVIG in BMT are prophylactic and suffer from variability in study design, type of IVIG and dosing regimens. Various effects on viral and bacterial infections and graft-versus-host disease (GVHD) have been reported but few if any have shown benefit in terms of improved patient survival. Moreover the immunomodulatory effect of immunoglobulin G preparations is frequently overlooked. With the exception of cytomegalovirus (CMV) pneumonitis, there is little evidence of benefit in the treatment of established infections and the relative benefits of hyperimmune preparations are poorly established. The development of haemopoietic growth factors has led to the widespread use of cytokines in BMT. The benefits of these agents both in the prevention of fever and infection and as adjuvants to standard antimicrobial therapy in established infection (e.g. invasive mycoses) are rapidly becoming apparent. Both human recombinant granulocyte-macrophage colony-stimulating factor (rhGM-CSF) and granulocyte colony-stimulating factor (rhG-CSF) have been shown to accelerate granulocyte recovery following BMT and reduce fever days, antibiotic usage and hospitalization. RhGM-CSF appears superior in these respects. The roles of interleukin 1 (IL1), IL3, IL6 and interferons are also under evaluation. As with the much publicised studies using anti-endotoxin antibodies as therapy in sepsis, there is little evidence of benefit in the few studies performed in BMT patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Immunotherapy and immunoprophylaxis in bone marrow transplantation. 756 Sep 54

Peripheral blood hematopoietic progenitors (PBHP) are capable of colony growth in vitro. The effect of stem cell factor (SCF), interleukin-6 (IL-6), and basic fibroblast growth factor (bFGF) on myeloid colony proliferation of PBHP was determined. PBHP purified by positive selection with CD34-specific antibody were plated in semisolid agarose with reported plateau doses of interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), and granulocyte colony-stimulating factor (G-CSF) to enhance myeloid colony growth. Experiments then were done to examine colony growth in response to SCF or with SCF and bFGF and/or IL6. SCF alone in the absence of any other growth factors did not support colony growth. SCF at a determined optimum concentration of 100 ng/mL added to the combination of IL-3, GM-CSF, and G-CSF enhanced colony growth and size relative to proliferation in response to the latter three factors alone (from 78 to 188 total colonies/10(4) PBHP plated and from 10 to 93 large [> 200 cells] colonies/10(4) PBHP plated). Furthermore, addition of bFGF and/or IL-6 to the combination of optimum concentrations of SCF, IL-3, GM-CSF, and G-CSF further enhanced colony number and size in a dose-dependent fashion. Using the optimum combination of all growth factors, we determined that the number of myeloid colony-forming PBHP in whole blood was similar between individuals at about three colonies per milliliter whole blood. We conclude that progenitors capable of responding to the early-acting growth factor, SCF, are represented in PBHP and that the number of circulating myeloid colony-forming PBHP is likely a regulated parameter that may have an important biologic function.
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PMID:Recombinant human stem cell factor enhances myeloid colony growth from human peripheral blood progenitors. 768 56

Cytokines manifest their function through alteration of gene expression. However, target genes for signals from cytokine receptors are largely unknown. We therefore searched for immediate-early cytokine-responsive genes and isolated a novel gene, CIS (cytokine inducible SH2-containing protein) which is induced in hematopoietic cells by a subset of cytokines including interleukin 2 (IL2), IL3, granulocyte-macrophage colony-stimulating factor (GM-CSF) and erythropoietin (EPO), but not by stem cell factor, granulocyte colony-stimulating factor and IL6. The CIS message encodes a polypeptide of 257 amino acids that contains an SH2 domain of 96 amino acids in the middle. To clarify the function of CIS in cytokine signal transduction, we expressed CIS in IL3-dependent hematopoietic cell lines under the control of a steroid-inducible promoter. The CIS product stably associated with the tyrosine-phosphorylated beta chain of the IL3 receptor as well as the tyrosine-phosphorylated EPO receptor. Forced expression of CIS by steroid reduced the growth rate of these transformants, suggesting a negative role of CIS in signal transduction. CIS induction requires the membrane-proximal region of the cytoplasmic domain of the EPO receptor as well as that of the common beta chain of the IL3, IL5 and GM-CSF receptor, whereas CIS binds to the receptor that is tyrosine phosphorylated by cytokine stimulation. Thus CIS appears to be a unique regulatory molecule for cytokine signal transduction.
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PMID:A novel cytokine-inducible gene CIS encodes an SH2-containing protein that binds to tyrosine-phosphorylated interleukin 3 and erythropoietin receptors. 779 8

Human autologous tumor-specific T-helper 2 (Th2) cells were investigated in melanoma tumor-infiltrating lymphocytes (TILs). Both a CD4+ T-cell line and its 5 potential T-cell clones established from TILs of a patient with metastatic melanoma produced significant levels of IL-4, IL-6, IL-10 and granulocyte-macrophage colony-stimulating factor (GM-CSF) in response to autologous, but not any of 12 allogeneic, melanoma cell lines. They also produced IL-3 and IL-8 but not IL-2, IFN-gamma, TNF-alpha or TNF-beta in response to autologous tumor cells. Furthermore, they showed autologous melanoma-specific cytotoxicity only in an 18-hr 51Cr-release assay. Specific IL-4, IL-6 or IL-10 production by the CD4+ M73 T-cell line and its clone was inhibited by anti-class II DR (but not anti-class I) MAb, whereas their specific cytotoxicity was inhibited by anti-class I (but not anti-class II) MAb. Anti-CD3 and -CD4 MAb (but not anti-CD8) abrogated both IL-4, IL6 and IL-10 production and cytotoxicity, while anti-IL-4 antibody did not inhibit cytotoxicity. CD4+ potential T-cell clones, but not CD8+ clones, that were established from freshly isolated TILs without in vitro sensitization by autologous tumor cells also produced IL-4, IL-6 and IL-10 but not IFN-gamma or tumor necrosis factor (TNF) alpha in an autologous tumor-specific fashion. These Th2 cells were neither reactive to EBV-B cells nor suppressive against CD8+ T-cell clones. PMA and PHA stimulated these potential T-cell clones, regardless of their specific lymphokine production, to produce IL-3, IL-4, IL-6, IL-8, IL-10, GM-CSF, TNF alpha and IFN-gamma. Our results demonstrate the presence of autologous tumor-specific Th2 cells at the melanoma sites.
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PMID:Characterization of autologous tumor-specific T-helper 2 cells in tumor-infiltrating lymphocytes from a patient with metastatic melanoma. 791 81

Proliferation of ramified microglia is a common phenomenon in brain pathology, but little is known about how this is regulated. In the current study, we examined the effect of different cytokines on the proliferation of ramified microglia in vitro using a combination of autoradiography for [3H]-thymidine and immunocytochemical techniques. Ramified microglia were obtained using a 10-day co-culture on top of a confluent astrocyte monolayer. Addition of macrophage colony-stimulating factor (MCSF), granulocyte-macrophage colony-stimulating factor (GMCSF), and interleukin-3 (IL3), stimulated the proliferation of ramified microglia, with a 7.2-fold, 3.5-fold, and 1.5-fold increase, respectively. Of all the other cytokines tested (IL1, IL2, IL4, IL6, IL10, interferon-gamma (IFNgamma), leukemia inhibitory factor (LIF), and tumor necrosis factor-alpha (TNFalpha) only IL1 strongly enhanced proliferation. However, this effect of IL1 was indirect and could be neutralized by antibodies against MCSF and GMCSF. IL2, IL4, IL10, TNFalpha, and IFNgamma inhibited microglial proliferation. The great number of inhibitory cytokines could point to the importance of containing microglial proliferation in the central nervous system.
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PMID:Proliferation of ramified microglia on an astrocyte monolayer: characterization of stimulatory and inhibitory cytokines. 927 47

Angiogenesis seems to be important in the pathogenesis of acute myelogenous leukemia (AML). The endothelial cell proliferation and microvessel formation are regulated by a wide range of soluble mediators, including angiogenin, angiopoietin-2, basic fibroblast growth factors, vascular endothelial growth factor (VEGF), VEGF-D, angiostatin and endostatin. In the present study, it has been investigated whether these mediators have an additional direct effect on the proliferation and cytokine release by native human AML blasts. AML cells derived from a large group of consecutive patients were investigated. All these mediators could alter the proliferation and cytokine release [interleukin (IL) 1beta, IL6, IL8, tumor necrosis factor alpha] for a minority of patients. Alteration of spontaneous proliferation by at least one mediator was detected in five of 38 patients; whereas, altered cytokine (Flt3-ligand, granulocyte-macrophage colony-stimulating factor, stem cell factor)-dependant proliferation was observed for 10 patients. Growth enhancement was most frequently observed, whereas growth inhibition was uncommon. The effects on AML blast proliferation were often dependant on or were modulated by the presence of the three hematopoietic growth factors. Based on the present results, it is concluded that angioregulatory mediators have additional growth-enhancing effects directly on the AML blasts for certain patients. However, based on the results from this investigation and previous studies it is suggested that their major contribution to the pathogenesis of AML is through their effects on regulation of bone marrow angiogenesis, and future studies of these mediators in AML should probably focus on these effects.
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PMID:Effects of angiogenic regulators on in vitro proliferation and cytokine secretion by native human acute myelogenous leukemia blasts. 1280 Dec 93

Human herpesvirus 6 (HHV-6) replication was evaluated during in vitro expansion of CD34-positive cells that were selected from 11 peripheral blood progenitor cell (PBPC) samples. In order to permit cellular differentiation towards the myeloid lineage, PBPCs were cultured for 14-21 days in a liquid, serum-free medium supplemented with interleukin 1 (IL1), IL3, IL6, granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor and stem-cell factor. Among the 10 cultures from HHV-6-seropositive patients, the late, alternatively spliced U100 viral mRNA was detected in five of them after PBPC culture for 14 or 21 days. Recovery of infectious virus from one of the expansions, associated with an increase of HHV-6 viral load and detection of the U100 spliced messenger, confirmed the occurrence of a complete replicative cycle. These data thus demonstrate for the first time that haematopoietic differentiation can lead to HHV-6 reactivation.
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PMID:Reactivation of human herpesvirus 6 during ex vivo expansion of circulating CD34+ haematopoietic stem cells. 1548 48

The objective of the present study was to examine the expression of Toll-like receptors (TLRs) by mouse uterine epithelial cells and to determine if stimulation of the expressed TLR induces changes in cytokine and/or chemokine secretion. Using RT-PCR, the expression of TLRs 1-6 by mouse uterine epithelial cells was demonstrated, with TLRs 7-9 expressed only periodically. In the absence of pathogen-associated molecular patterns, polarized uterine epithelial cells constitutively secrete interleukin (IL) 1A, cysteine-cysteine ligand (CCL) 2, IL6, granulocyte-macrophage colony-stimulating factor 2 (CSF2), tumor necrosis factor A (TNFA), CSF3, and IL8 in vitro, with levels of cytokines/chemokines secreted into the apical compartment being significantly greater than those released into the basolateral compartment. When added to the apical surface for 48 h before analysis, the TLR2-agonist Pam3Cys-Ser-(Lys)4 and TLR1/6-agonist peptidoglycan increased epithelial cell apical secretion of IL1A, CCL2, and IL6 and apical/basolateral bidirectional secretion of CSF2, TNFA, CSF3, and IL8 when compared to controls. The TLR3-agonist poly (I:C) significantly increased bidirectional secretion of CCL2, IL6, TNFA, and CSF2 and basolateral secretion of CSF3. Lastly, the TLR4-agonist lipopolysaccharide increased bidirectional secretion CCL2, CSF2, TNFA, CSF3, and IL8 and apical secretion of IL6. These results indicate that mRNAs for Tlr1 through Tlr6 are expressed by uterine epithelial cells and that treatment with specific TLR agonists alters the expression of key chemokines and proinflammatory cytokines that contribute to the defense of the uterus against potential pathogens.
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PMID:Expression of Toll-like receptors (TLR) and responsiveness to TLR agonists by polarized mouse uterine epithelial cells in culture. 1651 Aug 38


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