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 cytokines, interleukin-1 (IL-1) and tumor necrosis factor (TNF), induce a dose-dependent production of both granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte CSF (G-CSF) in cultured human synovial cells, as measured by immunoassay. With IL-1, significant levels of both CSFs were first detected within 6 to 12 hours, with a maximum reached 24 to 48 hours after commencement of stimulation. A synergistic effect was detected between IL-1 and TNF in production of both CSFs in these cells. No evidence was obtained for the IL-1-induced effect to be mediated by induction of endogenous TNF nor for the TNF-induced stimulation to involve IL-1. IL-1-stimulated synovial cells were shown to secrete biologically active GM-CSF and G-CSF, which were specifically inhibited by their respective monoclonal antibodies. The transcription inhibitor, actinomycin D, and protein synthesis inhibitor, cycloheximide, inhibited the increase in GM-CSF and G-CSF production induced by IL-1 and TNF. Finally, other cytokines, IL-3, interferon gamma (IFN gamma), IL-2, platelet-derived growth factor (PDGF), epidermal growth factor (EGF) and transforming growth factor alpha (TGF alpha), failed to stimulate either GM-CSF or G-CSF production, whether alone or in the presence of IL-1. These results suggest that cytokine-stimulated synovial fibroblasts may be a major source of intraarticular CSF production in the joints of patients with inflammatory arthritis; as a result, monocyte/macrophages and granulocytes may be activated, leading to perpetuation of the inflammation and destructive events occurring in these lesions.
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PMID:Cytokine regulation of colony-stimulating factor production in cultured human synovial fibroblasts: I. Induction of GM-CSF and G-CSF production by interleukin-1 and tumor necrosis factor. 170 Jul 31

We have previously demonstrated a constitutive expression of transforming growth factor alpha (TGF-alpha) in normal human blood eosinophils, both at the mRNA and protein level. This may indicate a novel function of the eosinophil, the regulation of which has not been clarified. Therefore human white blood cells (WBC) were treated with potential regulators of eosinophil function. Northern blot analysis demonstrated that human recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin-3 (IL-3) caused a time and dose-dependent 2- to 3-fold increase of TGF-alpha mRNA levels, in relation to incubation in the absence of cytokine; maximal response was attained within 4 h of incubation. In contrast, IL-5 failed to influence the expression of the TGF-alpha gene. In situ analysis of GM-CSF- or IL-3-stimulated cells showed that eosinophils remained the sole cell type expressing TGF-alpha mRNA. However, whereas GM-CSF significantly induced, within 1 h, release of immunoreactive TGF-alpha protein, IL-3 was insufficient in this respect. In conclusion, our findings indicate that expression of TGF-alpha gene and protein in normal blood eosinophils is differently regulated by GM-CSF and IL-3.
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PMID:Transforming growth factor alpha expression in normal human blood eosinophils: differential regulation by granulocyte-macrophage colony-stimulating factor and interleukin-3. 751 73

The effects of Porphyromonas gingivalis lipopolysaccharide (P-LPS) and Escherichia coli lipopolysaccharide (E-LPS) on the gene expression and production of inflammatory cytokines of human periodontal ligament fibroblasts (HPLF) were examined by a Northern (RNA blot) assay and enzyme-linked immunosorbent assay, respectively. mRNAs for interleukin-6 (IL-6), IL-8, and transforming growth factor beta (TGF-beta) were detected in HPLF cells, but IL-1 alpha, IL-1 beta, tumor necrosis factor alpha, transforming growth factor alpha, and granulocyte-macrophage colony-stimulating factor were not detected by reverse transcription-PCR. The expression of TGF-beta mRNA was not influenced by either LPS. P-LPS (1 to 10 micrograms/ml) and E-LPS (100 micrograms/ml) markedly stimulated the expression of IL-6 and IL-8 mRNAs compared with the control. The synthesis of IL-6 and IL-8 was also stimulated by 10 and 100 micrograms of both LPSs per ml, but IL-8 synthesis was not stimulated with E-LPS at 1 microgram/ml. Secretion of IL-6 and IL-8 into the culture medium was detected at 6 and 3 h, respectively, after exposure to P-LPS (10 micrograms/ml). These findings suggested that P. gingivalis leads to periodontal tissue destruction and alveolar bone resorption through IL-6 and IL-8 released from HPLF cells stimulated with its LPS.
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PMID:Inflammatory cytokine gene expression in human periodontal ligament fibroblasts stimulated with bacterial lipopolysaccharides. 764 93

The purpose of this study was to determine the mRNA expression level of multiple cytokine and growth factor genes in human malignant melanoma. Melanoma cells were isolated from several surgical specimens, adapted to growth in culture, characterized for their ability to produce experimental metastases in nude mice, and assessed for cytokine and growth factor steady-state gene expression. Highly metastatic in vivo- and in vitro-derived variants isolated from a single melanoma, A375, were also analyzed. Northern blot analyses revealed that all melanomas analyzed constitutively expressed steady-state mRNA transcripts for the growth and angiogenic factors, basic fibroblast growth factor (bFGF), and transforming growth factor alpha (TGF-alpha), which correlated with metastatic propensity. Only one highly metastatic melanoma, TXM-1, originally isolated from a lymph node metastasis, expressed mRNA transcripts specific for monocyte chemotactic and activating factor (MCAF) and granulocyte-macrophage colony-stimulating factor (GM-CSF). Similarly, of the nine melanomas examined, only TXM-1 expressed interleukin (IL)-1 alpha, IL-1 beta, and IL-6, important immunomodulatory cytokines. These data demonstrate the differential and heterogeneous expression of cytokine and growth factor genes in human malignant melanoma.
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PMID:Heterogeneity of cytokine and growth factor gene expression in human melanoma cells with different metastatic potentials. 764 37

We demonstrate the constitutive expression of interleukin 6 (IL-6), IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF), epidermal growth factor (EGF), transforming growth factor alpha (TGF-alpha) and epidermal growth factor receptor (EGFR) in normal kidney cells, and in the majority of renal oncocytomas, papillary and non-papillary renal cell carcinomas (RCCs) by reverse transcriptase polymerase chain reaction (RT-PCR) technique. No expression of IL-6 and TGF-alpha and variable expression of GM-CSF, IL-8, EGF and EGFR was seen in chromophobe RCCs. The lack of expression of IL-6 and TGF-alpha might be correlated with the growth pattern, poor vascularity and low malignancy of chromophobe RCCs.
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PMID:Lack of interleukin 6 (IL-6) and transforming growth factor alpha (TGF-alpha) expression in chromophobe renal cell carcinomas. 982 Jan 73