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)

Recombinant human tumor necrosis factor-alpha (TNF-alpha) was found to stimulate the growth of CMK, a human megakaryoblastic leukemia cell line. This stimulatory effect of TNF-alpha was blocked by anti-TNF-alpha antibody, but antibodies to recombinant human interleukin 3, granulocyte-macrophage colony-stimulating factor and interleukin 6 (all growth factors for CMK cells) did not reduce the stimulatory effect of TNF-alpha. Scatchard analysis showed that CMK cells expressed TNF-alpha receptors on the cell surface. The growth of CMK cells was also stimulated by lymphotoxin, which shares the same receptor as TNF-alpha. These results suggest that TNF-alpha stimulated the growth of CMK cells directly via its specific receptor.
 ...
PMID:Stimulatory effect of tumor necrosis factor-alpha on the growth of CMK, a human megakaryoblastic leukemia cell line. 131 36

The repertoire of cytokine and cytokine receptor mRNA expressed by unstimulated human thymocytes and thymic stromal cells was explored by a quantitative polymerase chain reaction (PCR) using sequence specific internal standards. Of the 18 cytokines tested we found a considerable overlap in the expression of cytokines by human thymocytes and by thymic stromal cells; both cell types express the mRNA for interleukin-1 beta(IL-1, IL-6, IL-7 and tumour necrosis factor-alpha (TNF-alpha). However, there are substantial differences in the levels of cytokine mRNA expressed in these two types of cells as revealed by the quantitative PCR assay. Stromal cells express considerably higher levels of IL-1 beta and IL-6 than thymocytes (14- and 27-fold respectively). In addition, a number of cytokines such as lymphotoxin and interferon-gamma (IFN-gamma), are expressed exclusively in thymocytes whereas others such as stem cell factor (SCF), IL-1 receptor antagonist-2 (IRAP-2) and granulocyte-macrophage colony-stimulating factor (GM-CSF) are produced only in stromal cells. There is a complete overlap in the expression of a group of cytokine receptors tested in thymocytes and thymic stromal cells; these include IL-1R, IL-2R, IL-6R, IL-7R, TNFR and stem cell growth factor receptor (c-KIT). The expression of specific cytokines by thymic stromal cells and the parallel expression of their receptors on thymocytes under physiological conditions, support the hypothesis that these cytokines participate in paracrine interactions between these two cell populations during thymocyte differentiation.
 ...
PMID:Expression of cytokines and their receptors by human thymocytes and thymic stromal cells. 133 59

Fc receptors (FcR) are of importance in immune and inflammatory reactions. FcR expression as mRNA and surface protein was therefore examined in the myelomonocytic cell line, U937, after stimulation with phorbol ester (PMA), in the presence of seven different cytokines (interferon-gamma [IFN gamma], IFN alpha, granulocyte-macrophage colony-stimulating factor [GM-CSF], tumour necrosis factor-alpha [TNF alpha], TNF beta, interleukin-beta [IL-1 beta], IL-2) or dexamethasone. HLA class I and CD11b expression were also examined. Cell surface expression of FcRI and II was measured by flow cytometry using monoclonal antibodies, and the mRNA of FcRII was measured with cDNA or oligonucleotide probes. The major findings were: PMA increased cell surface FcRI, FcRII and CD11b, but decreased HLA; PMA caused a fivefold increase in all three FcRII RNA transcripts (2.5, 1.5 and 0.9 kb) in Northern analysis; IFN gamma, IFN alpha and GM-CSF increased the expression of FcRI and II, and there was no effect with IL-1 beta, IL-2, TNF alpha or TNF beta (only GM-CSF increased the expression of CD11b); all cytokines further increased FcRI and FcRII expression in the presence of PMA; HLA expression was also increased in the presence of PMA, IFN alpha and IFN gamma; dexamethasone reduced the levels of FcRI and II in cells stimulated with PMA with or without cytokines. Thus stimulatory agents and cytokines can alter the expression of surface Fc gamma R and mRNA encoding FcRI or II, providing potential control mechanisms for the modulation of these receptors in inflammatory responses.
 ...
PMID:Effects of PMA, cytokines and dexamethasone on the expression of cell surface Fc receptors and mRNA in U937 cells. 135 19

Tumor necrosis factor (TNF)-alpha and TNF-beta have multiple effects on human acute myeloid leukemia (AML) cells in vitro, including (1) synergistic stimulation of proliferation with interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) and upregulation of interleukin-3 (IL-3) and GM-CSF receptors; (2) inhibition of granulocyte-CSF (G-CSF)-induced growth and rapid downmodulation of G-CSF receptors; and (3) induction of autocrine growth. Recently, two distinct TNF receptors (TNF-Rs), TNF-R(p55) and TNF-R(p75), have been identified. In this study, we show that both receptor types may be expressed by AML blasts. It has been investigated whether the different effects of TNF on AML blasts can be explained by differential activation of the distinct TNF-R structures. For this purpose, we used the monoclonal antibodies HTR-1 and HTR-9, specifically recognizing TNF-R(p55), and UTR-1, specific for TNF-R(p75). TNF-(alpha and -beta) mediated synergistic activation with IL-3/GM-CSF, upregulation of IL-3/GM-CSF receptors, inhibition of G-CSF-induced growth, and rapid downmodulation of G-CSF receptors exclusively result from activation of TNF-R(p55). In certain cases in which TNF-alpha, rather than TNF-beta, induces AML growth through an autocrine mechanism, both TNF-R(p55) and (p75) are involved. These data indicate that the variety of TNF responses observed in AML can only be partially explained by differential activation of the TNF-R(p55) and (p75) structures, and that TNF-R(p55) on AML blasts can transduce both positive (synergism with IL-3/GM-CSF) and negative regulatory signals (inhibition of G-CSF-induced proliferation) following TNF activation.
 ...
PMID:Involvement of tumor necrosis factor (TNF) receptors p55 and p75 in TNF responses of acute myeloid leukemia blasts in vitro. 138 4

Cytokine release at the cartilage/pannus junction (CPJ) may be involved in cartilage destruction and tissue repair in rheumatoid arthritis (RA). Tissue samples of CPJ from 12 RA patients were examined for the presence of cytokines using immunohistochemical techniques with immunoaffinity purified F(ab')2 antibodies raised against recombinant human cytokines. Twenty-four areas of distinct CPJ at which a discrete junction between cartilage and overlying pannus exists were observed. In all specimens, tumour necrosis factor (TNF)-alpha, interleukin (IL)-1 alpha. IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF) and transforming growth factor (TGF)-beta 1 were detected in cells in pannus particularly along the surface of cartilage and at the site of cartilage erosion. Double immunofluorescence staining showed that most cytokine containing cells also labelled with a macrophage marker (CD68). About 50% of blood vessel endothelial cells stained for GM-CSF. Twelve areas of diffuse fibroblastic CPJ, at which an indistinct margin is seen between cartilage and pannus were examined. At this site, TGF-beta 1 was the only cytokine detected in fibroblast-like cells. None of these cytokines were detected in synovial tissue at the normal synovium/cartilage junction. Chondrocytes from all 11 normal specimens as well as those from RA patients stained for IL-1 alpha, TNF-alpha, IL-6, GM-CSF and TGF-beta 1, especially those close to subchondral bone. However, IL-1 beta, interferon-gamma and lymphotoxin were not detected in either the normal synovium/cartilage junction or rheumatoid CPJ.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Detection of cytokines at the cartilage/pannus junction in patients with rheumatoid arthritis: implications for the role of cytokines in cartilage destruction and repair. 139 70

In the present study, we show by Northern blot analysis and enzyme linked immunosorbent assay that the Hodgkin's disease (HD)-derived cell lines HDLM-2 and KM-H2 express a variety of cytokine genes either constitutively or upon induction with phorbol ester 12-O-tetradecanoylphorbol-13-acetate. Cytokine genes expressed by HD-derived lines include granulocyte-macrophage colony-stimulating factor (CSF), macrophage-CSF, interleukin (IL)-1-alpha, IL-3, IL-5, IL-6, IL-8, leukemia inhibitory factor, tumor necrosis factor-alpha, tumor necrosis factor-beta, and transforming growth factor-beta, while transcripts and the corresponding proteins for granulocyte-CSF, IL-1-beta, IL-2, IL-4, IL-7, IL-10, and the JE/macrophage chemoattractant and activating factor gene were not detectable in cytoplasmic RNA and culture supernatants obtained from both lines. In addition, IL-2 receptor (R) p55 and macrophage-CSF R (c-fms) genes were expressed by both lines. HDLM-2, but not KM-H2 cells, exhibited the IL-6 R p80 and the IL-2 R p75 chain. Analysis of nuclear proteins that bind to oligonucleotides containing the consensus sequences of the transcription factors activation protein 1, nuclear factor (NF) kappa B, and NFAT 1 revealed a pattern for HD lines resembling that of activated T-cells: HDLM-2 and KM-H2 cells constitutively expressed NF binding to the NF of activated T-cells (type 1), previously described to be T-cell specific. In addition, NF kappa B-binding proteins obtained from both lines showed, in electrophoretic mobility shift assays, the same migration pattern as T-cell-derived proteins but differed from monocyte- and B-cell-derived proteins. UV cross-linking experiments confirmed that NF kappa B-binding proteins of M(r) 85,000, 75,000, and 50,000/55,000 were detectable in nuclear extracts obtained from T-cells and both HD lines, while monocytes and B-cells displayed the M(r) 50,000/55,000 and 75,000 NF kappa B complex only. Both HD lines also constitutively expressed transcripts for c-fos and c-jun, which are involved in heterodimeric formation of the transcription factor activation protein 1, as well as for the NF kappa B/KBF1 gene.
 ...
PMID:Expression of cytokine genes, cytokine receptor genes, and transcription factors in cultured Hodgkin and Reed-Sternberg cells. 159 93

The recent demonstration of the ability of human polymorphonuclear neutrophils (PMN) to secrete various cytokines in response to the granulocyte activator granulocyte-macrophage colony-stimulating factor (GM-CSF) but not to other cytokines, has led to the identification of PMN as biosynthetically active cells. In this study we have investigated the ability of PMN to secrete interleukin-6 (IL-6), a molecule known to be involved in inflammatory reactions. Using RNA blotting analysis and bioassays, we show that PMN could be induced to synthesize transcripts specific for IL-6, indistinguishable in size from IL-6 mRNA produced by activated human macrophages. Consequently, PMN released IL-6-like activity into their culture supernatants that could be neutralized by monospecific anti-IL-6 antibody. Interleukin-6 secretion by PMN, however, required previous stimulation with GM-CSF or tumor necrosis factor-alpha (TNF-alpha), whereas other cytokines, including interleukin-3 (IL-3), granulocyte-CSF (G-CSF), macrophage-CSF (M-CSF), interferon gamma (IFN-gamma), and lymphotoxin (LT), failed to induce IL-6 mRNA accumulation and protein secretion by PMN. Similar to GM-CSF and TNF-alpha, other compounds, including the inhibitor of protein synthesis cyclohexemide (CHX), endotoxin (Escherichia coli-derived lipopolysaccharide), and phorbol myristate acetate (PMA) (but not the chemoattractant N-formyl-methionyl-leucyl-phenylalanine [FMLP]), induced detectable levels of IL-6 transcripts in PMN.
 ...
PMID:Inducible production of interleukin-6 by human polymorphonuclear neutrophils: role of granulocyte-macrophage colony-stimulating factor and tumor necrosis factor-alpha. 169 93

The immune response at the molecular level is characterized by a carefully coordinated interplay of both cytokine production and receptor induction. The regulation of these molecules including the closely related tumor necrosis factors alpha (TNF) and beta (lymphotoxin, LT) is still incompletely understood. We have examined the effects of various cytokines on the expression of TNF and LT mRNA in human peripheral blood mononuclear cells (PBMC). Northern blot analysis with total cellular RNA from mixed populations of PBMC revealed that genes coding for TNF and LT were not spontaneously expressed. Treatment of PBMC with recombinant interleukin (IL)-2 resulted in a high level expression of TNF and LT mRNA. Whereas IL-1 beta was equally effective as IL-2 in inducing both TNF and LT mRNA, granulocyte-macrophage colony-stimulating factor selectively induced only TNF mRNA. Both TNF and LT mRNA were minimally induced by IL-1 alpha, IL-3, interferon (IFN)-alpha, or IFN-gamma. Similarly TNF alone had little effect on induction of TNF and LT mRNA. In conjunction with IL-2, cytokines such as IFN-alpha, IFN-gamma, or TNF did not interfere with IL-2 induction of TNF and LT mRNA. Interestingly, IL-4 in combination with IL-2 inhibited the IL-2-driven induction of TNF and LT mRNA. This inhibitory effect of IL-4 was also observed at the level of TNF and LT protein secretion. Furthermore, IL-4 was also inhibitory of IL-2-mediated induction of Tac mRNA in PBMC. These results extend the interrelationship of cytokine regulation of TNF and LT expression. In particular, they reveal the previously unrecognized function of IL-4 in antagonizing the IL-2 induction of TNF, LT, and Tac mRNA in PBMC.
 ...
PMID:Cytokine regulation of tumor necrosis factor-alpha and -beta (lymphotoxin)-messenger RNA expression in human peripheral blood mononuclear cells. 169 66

The hemopoietic CSF, granulocyte-macrophage CSF (GM-CSF) and granulocyte CSF (G-CSF), are cytokines that mediate the clonal proliferation and differentiation of progenitor cells into mature macrophages and/or granulocytes. We have employed an all-human cell culture system, specific ELISA for GM-CSF and G-CSF, and Northern analysis to investigate whether chondrocytes are a potential source of CSF in rheumatoid disease. We report that human rIL-1 stimulated in a dose-dependent manner the production of GM-CSF and G-CSF by human articular cartilage and chondrocyte monolayers in organ and cell culture, respectively. Increased levels of the CSF Ag were detected after 2 to 8 h stimulation with IL-1, and the optimum dose of IL-1 was 10 to 100 U/ml (0.06 to 0.6 nM IL-1 alpha; 0.02 to 0.2 nM IL-1 beta); neither CSF was detectable in nonstimulated cultures nor in IL-1-stimulated cultures treated with actinomycin D or cycloheximide, indicating the requirement for de novo RNA and protein synthesis. The IL-1-mediated increase in GM-CSF could also be inhibited by the corticosteroid, dexamethasone, but not by the cyclo-oxygenase inhibitor, indomethacin. Although having little effect when tested alone, TNF-alpha and lymphotoxin (TNF-beta) could synergize with IL-1 for the production of GM-CSF. Basic fibroblast growth factor, platelet-derived growth factor, and IFN-alpha and IFN-gamma each had no effect on GM-CSF levels. Results obtained by Northern analysis of chondrocyte total RNA reflected those found for the CSF Ag, namely that CSF mRNA levels were elevated in response to IL-1, but not TNF, and that there was synergy between these two cytokines. We propose that chondrocyte CSF production in response to IL-1, and the concurrent destruction of cartilage by IL-1, could provide a mechanism for the chronic nature of rheumatoid disease.
 ...
PMID:Human articular cartilage and chondrocytes produce hemopoietic colony-stimulating factors in culture in response to IL-1. 171 78

We have studied cytokine expression by the human bladder carcinoma cell line 5637 using a cDNA-PCR procedure. Transcripts for interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-6, IL-7, IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF), G-CSF, M-CSF, tumor-necrosis factor-alpha (TNF-alpha), and TNF-beta were constitutively present, whereas IL-3, IL-4, IL-5, and IL-9 mRNA sequences could not be detected. This expression pattern was not altered after 12-O-tetradecanoyl-phorbol-13-acetate (TPA) stimulation (4 and 8 h) of 5637 cells. Relative expression levels of cytokines were assessed by limiting dilution of the cDNA pool. This procedure proved to be a semiquantitative technique when compared to Northern blot analysis.
 ...
PMID:Cytokine production by the bladder carcinoma cell line 5637: rapid analysis of mRNA expression levels using a cDNA-PCR procedure. 188 17


1 2 3 4 5 6 Next >>