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)

The human granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor consists of 2 glycoprotein subunits, GMRalpha and GMRbeta. GMRalpha in isolation binds to GM-CSF with low affinity. GMRbeta does not bind GM-CSF by itself, but forms a high-affinity receptor in association with GMRalpha. Previously, it was found that N-glycosylation of GMRalpha is essential for ligand binding. The present study investigated the role of N-glycosylation of the beta subunit on GM-CSF receptor function. GMRbeta has 3 potential N-glycosylation sites in the extracellular domain at Asn58, Asn191, and Asn346. Single mutants and triple mutants were constructed, converting asparagine in the target sites to aspartic acid or alanine. A single mutation at any of the 3 consensus N-glycosylation sites abolished high-affinity GM-CSF binding in transfected COS cells. Immunofluorescence and subcellular fractionation studies demonstrated that all of the GMRbeta mutants were faithfully expressed on the cell surface. Reduction of apparent molecular weight of the triple mutant proteins was consistent with loss of N-glycosylation. Intact N-glycosylation sites of GMRbeta in the extracellular domain are not required for cell surface targeting but are essential for high-affinity GM-CSF binding.
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PMID:High-affinity binding to the GM-CSF receptor requires intact N-glycosylation sites in the extracellular domain of the beta subunit. 1082 16

The effect of cytokine adjuvancy on a bovine viral diarrhoea virus (BVDV) DNA vaccine expressing the major glycoprotein E2 was investigated in mice. Murine interleukin-2 (IL-2) and granulocyte-macrophage colony-stimulating factor (GM-CSF) were chosen for their potential ability to enhance the humoral and cellular immune responses involved in protection against BVDV. Both cytokines, co-administered as separate plasmid constructs, had a marked effect on ELISA and neutralising antibody titres, improving the spectrum of neutralisation induced by the E2 DNA vaccine, as demonstrated in heterologous neutralisation assays. The predominance of IgG2a isotypes, in sera from all DNA injected groups, indicated a Th1 biased immune response. Antigen specific proliferation of murine splenocytes from immunised mice was enhanced by cytokine co-administration, with the highest stimulation indexes observed in the group co-injected with the GM-CSF construct. These results obtained in the mouse (Balb/c; H2-kd) animal model demonstrate the value of the two cytokines as adjuvants for the E2 DNA vaccine. The need for an adjuvant in this system was emphasised by the MHC restriction observed when C57BL/6 mice (H2-kb) were immunised with the E2 DNA construct. Antibody levels were dramatically lower in this mouse strain.
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PMID:Cytokine adjuvancy of BVDV DNA vaccine enhances both humoral and cellular immune responses in mice. 1145 49

Black-pigmented anaerobic bacteria, such as Porphyromonas gingivalis and Prevotella intermedia, are amongst the predominant bacteria in periodontal pockets and have been implicated in periodontal diseases. To elucidate the roles of gingival keratinocytes, which are the first cells encountered by oral bacteria in periodontal diseases, human gingival keratinocytes in primary culture were stimulated with cell-surface components of P gingivalis and Pr. intermedia. A glycoprotein fraction from Pr. intermedia (PGP) clearly augmented the release of interleukin-8, granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor, as determined by enzyme-linked immunosorbent assay. This PGP also induced expression of intercellular adhesion molecule-1 (ICAM-1), as determined by flow cytometry. The augmentation of mRNA expression for these molecules was also confirmed by reverse transcription PCR. In contrast, lipopolysaccharide (LPS) from Pr. intermedia and Escherichia coli was completely inactive in these assays. LPS fraction and purified fimbriae from P gingivalis exhibited weak activities. Cytokine production and ICAM-1 expression by gingival keratinocytes might cause accumulation and activation of neutrophils in the epithelium and, therefore, may be involved in the initiation and development of inflammation in periodontal tissues.
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PMID:Activation of human gingival epithelial cells by cell-surface components of black-pigmented bacteria: augmentation of production of interleukin-8, granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor and expression of intercellular adhesion molecule 1. 1180 Apr 68

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a glycoprotein that stimulates the production of granulocytes, macrophages, and white blood cells. Secretion of human GM-CSF from cell suspension cultures of genetically modified tobacco has been facilitated using natural mammalian leader sequences. At the mid-exponential growth phase (day 4 after the initiation of cell suspension culture), GM-CSF was detected in the medium at a maximum concentration of 180 microg l(-1). However, the secreted GM-CSF was unstable in the medium, and rapidly degraded after day 5. In order to stabilize the secreted GM-CSF, three stabilizing polymers were tested, polyethylene glycol, polyvinylpyrrolidone and gelatin. Gelatin was the most effective in stabilizing the secreted GM-CSF. Following the addition of 5% (w/v) gelatin, the maximum GM-CSF concentration reached 783 microg l(-1), a 4.6-fold increase over control.
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PMID:Increased production of human granulocyte-macrophage colony stimulating factor (hGM-CSF) by the addition of stabilizing polymer in plant suspension cultures. 1204 49

Carcinoembryonic antigen (CEA) is a glycoprotein that is normally expressed in certain parts of the body and commonly overexpressed in most carcinomas of the colon, rectum, breast, lung, pancreas, and gastrointestinal tract. Increased expression of CEA promotes increased intercellular adhesions, which may lead to metastasis. Carcinoembryonic antigen is often used as a serologic marker of malignancy because of its overexpression in cancer as well as its measurability in serum. However, because CEA is normally expressed in the body, the immune system commonly becomes tolerant to it. If this tolerance can be overcome without leading to autoimmune disease, CEA vaccination therapy could be immensely beneficial to cancer patients. A number of preclinical and clinical studies have been conducted on the use of recombinant CEA-vaccinia virus vaccines and recombinant ALVAC-CEA vaccines. In general, the vaccines have been well tolerated and effective at inducing CEA-specific cytotoxic T-cell responses, especially when used in the presence of the T-cell costimulatory molecule B7.1. "Prime and boost" techniques combining both types of vaccines and the addition of cytokines such as granulocyte-macrophage colony-stimulating factor have resulted in enhanced T-cell responses. The combination of vaccinia or ALVAC vaccines with a triad of costimulatory molecules (B7.1, ICAM-1, and LFA-3) has also stimulated significant T-cell increases. This review summarizes these studies and discusses the role of CEA in cancer immunotherapy.
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PMID:Carcinoembryonic antigen-based vaccines. 1288 10

Haematopoiesis is regulated by a wide variety of glycoprotein hormones, including stem cell factor, granulocyte-macrophage colony-stimulating factor, thrombopoietin and IL-3. These haematopoietic growth factors (HGFs) share a number of properties, including redundancy, pleiotropy, autocrine and paracrine effects, receptor subunit oligomerisation and similar signal transduction mechanisms, yet each one has a unique spectrum of haematopoietic activity. Ongoing studies with knockout mice have discovered previously unrecognised physiological roles for HGFs, linking haematopoiesis to innate immunity, pulmonary physiology and bone metabolism. The regulation of stem cells by HGFs within niches of the bone marrow microenvironment is now well recognised and similar mechanisms appear to exist in the regulation of other stem cell compartments. Alternative signalling strategies, other than tyrosine kinase activation and phosphotyrosine cascades, may account for some of the more subtle differences between HGFs. Accumulating evidence suggests that some, but not all, HGF receptors can transduce a genuine lineage-determining signal at certain points in haematopoiesis. Further studies, primarily at the receptor level, are needed to determine the mechanisms of instructive signalling, which may include phosphoserine cascades. Novel haematopoietic regulators, as well as the development of biological therapies, including growth factor antagonists and peptide mimetics, are also discussed.
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PMID:Regulation of haematopoiesis by growth factors - emerging insights and therapies. 1517 69

In order to study the effect of human granulocyte-macrophage colony-stimulating factor (hGM-CSF) as active cytokine through orally administration, we expressed hGM-CSF within silkworm pupae bioreactor. The purified rhGM-CSF named as BmrhGM-CSF is characterized as 29kDa glycoprotein, and its biological activity was measured both in vitro and in vivo. We found out BmrhGM-CSF could stimulate the colony formation of human bone marrow cells in a dose-dependent manner whether which were treated with or without gamma-ray 24h before. The ability of colony formation induced by BmrhGM-CSF is negatively correlated with gamma-ray intensity. As soon as 15min post oral administration with BmrhGM-CSF labeled with (125)I, an approximately 20kDa protein fragment was detected within mice blood by SDS-PAGE followed by autoradiography. In blood sample of test mice, a protein was also recognized by anti-hGM-CSF antibody using ELISA. The immunohistochemical analysis showed that BmrhGM-CSF was detected within intestinal histiocyte. This indicated it might be absorbed into blood via intestinal microvillus. Pharmacokinetics analysis after orally administered BmrhGM-CSF in animal model of leucopenia including mice, Beagle dogs and macaques showed that: (1) BmrhGM-CSF promoted the CFU-S formation in mice spleen and the synthesis of DNA in bone marrow cells of mice; (2) BmrhGM-CSF induced bone marrow karyocyta granulocyte growth significantly in both macaques and Beagle dogs compared to the negative control group. On the 9th day of orally administration, the animal WBC significantly increased in a dose-dependant manner, in which neutrophilic granulocyte was predominant. The WBC level of dogs in high dose group was about 1.5x10(9)cells/L more than that in the negative control. And the bone marrow smear revealed that the percents of both myloblast and progranulocyte in WBC in the hGM-CSF group were obviously higher than those in the negative control. These results proved that BmrhGM-CSF, a 29kDa glycoprotein expressed by Silkworm pupae bioreactor, could bring into the effect as active cytokine through oral administration.
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PMID:Can 29kDa rhGM-CSF expressed by silkworm pupae bioreactor bring into effect as active cytokine through orally administration? 1661 62

Several DNA constructs containing the spring viraemia of carp virus (SVCV) glycoprotein (G) gene were investigated for their ability to induce protection against SVCV following injection into myofibres. The constructs were pooled into four groups and co-injected with a plasmid encoding murine granulocyte-macrophage colony-stimulating factor. Group 1 contained one full-length and two truncated G constructs under the control of the cytomegalovirus (CMV) promoter. Group 2 contained full-length constructs with the CMV promoter, the simian virus 40 promoter and a muscle-specific promoter. Group 3 contained constructs in which the G-gene was fused with a second gene in order to improve secretion of the G-protein or to enhance destruction of transfected myocytes by T cells. Group 4 contained constructs with the CMV-Intron A promoter in plasmids with or without CpG motifs. A small-scale trial in goldfish showed that antibody responses in at least half the fish were induced by three injections of plasmids from Groups 1 and 3 whereas T-cell like responses with stimulation indices of above 3 were induced in at least half the fish by Groups 2 and 4. A single-dose of each plasmid mix was then used to protect carp in a large-scale trial. Following challenge with a heterologous strain of SVCV that killed 64% of fish, the strongest protection was observed in carp that received the full length G-gene expressed by two plasmids driven by the CMV-Intron A promoter (Group 4), with a relative percentage survival of 48% (p=0.00008).
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PMID:DNA vaccination can protect Cyprinus Carpio against spring viraemia of carp virus. 1665 Sep 15

Neutropenia and its subsequent infectious complications represent the most common dose-limiting toxicity of cancer chemotherapy. Febrile neutropenia (FN) occurs with common chemotherapy regimens in 25 to 40 % of treatment-naive patients, and its severity depends on the dose intensity of the chemotherapy regimen, the patient's prior history and comorbidities. Neutropenia is associated with the risk of life-threatening infections as well as chemotherapy dose reductions and delays that may compromise treatment outcome. One of the first, most important and sustained applications of recombinant DNA technology in medicine was the cloning and introduction into clinical practice of several glycoprotein factors involved in the regulation of hematopoiesis. Colony-stimulating factors (CSFs) such as granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) are now an integral part of the prevention of potentially life-threatening FN. Important uses of CSFs in oncology are prevention of FN after chemotherapy, treatment of FN, collection of CSF-mobilised peripheral stem cells and support following peripheral stem cells transplantation. This article reviews the data supporting the clearly clinical applications of CSFs in oncology.
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PMID:[G-CSF in oncology]. 1677 24

Ebola virus causes outbreaks of severe viral hemorrhagic fever with high mortality in humans. The virus is highly contagious and can be transmitted by contact and by the aerosol route. These features make Ebola virus a potential weapon for bioterrorism and biological warfare. Therefore, a vaccine that induces both systemic and local immune responses in the respiratory tract would be highly beneficial. We evaluated a common pediatric respiratory pathogen, human parainfluenza virus type 3 (HPIV3), as a vaccine vector against Ebola virus. HPIV3 recombinants expressing the Ebola virus (Zaire species) surface glycoprotein (GP) alone or in combination with the nucleocapsid protein NP or with the cytokine adjuvant granulocyte-macrophage colony-stimulating factor were administered by the respiratory route to rhesus monkeys--in which HPIV3 infection is mild and asymptomatic--and were evaluated for immunogenicity and protective efficacy against a highly lethal intraperitoneal challenge with Ebola virus. A single immunization with any construct expressing GP was moderately immunogenic against Ebola virus and protected 88% of the animals against severe hemorrhagic fever and death caused by Ebola virus. Two doses were highly immunogenic, and all of the animals survived challenge and were free of signs of disease and of detectable Ebola virus challenge virus. These data illustrate the feasibility of immunization via the respiratory tract against the hemorrhagic fever caused by Ebola virus. To our knowledge, this is the first study in which topical immunization through respiratory tract achieved prevention of a viral hemorrhagic fever infection in a primate model.
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PMID:Successful topical respiratory tract immunization of primates against Ebola virus. 1742 68


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