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)

Protein antigens with both allergenic and immunoprotective properties represent appropriate molecules to study IgE and IgG regulation. We have established a panel of T cell clones specific to bee venom phospholipase A2 (PLA) from human individuals allergic, hyposensitized or immune (protected) to bee sting. All clones obtained were CD3+, CD4+ and expressed alpha, beta T cell receptor. Depending on the T cell clone, maximal stimulation required 1 to 100 micrograms/ml of PLA, and the addition of interleukin (IL)-2 and/or IL-4 increased their antigen-dependent proliferation. Following antigen stimulation, the clones produced IL-4, interferon-gamma (IFN-gamma) and granulocyte-macrophage colony-stimulating factor. Most clones also produced tumor necrosis factor alpha (TNF-alpha) and tumor necrosis factor beta (TNF-beta), and some produced IL-5 and/or IL-2. Both absolute and relative amounts of secreted cytokines depended on the antigen concentration. At low antigen doses, IL-4 was produced but little or not IFN-gamma, whereas at higher PLA concentrations significant amounts of both IL-4 and IFN-gamma were obtained. Thus, these PLA-specific T cell clones could be classified according to the changes in the ratio of IL-4/IFN-gamma production in response to increasing antigen concentrations. Clones derived from allergic and hyposensitized individuals required higher critical amounts of antigen for IFN-gamma induction, and expressed increasing IL-4/IFN-gamma ratios with increasing concentrations of PLA. Modulation of cytokine patterns by the dose of the antigen may be a driving force for IgE or IgG formation resulting in allergy or immunoprotection.
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PMID:Bee venom phospholipase A2-specific T cell clones from human allergic and non-allergic individuals: cytokine patterns change in response to the antigen concentration. 160 Oct 30

Erythroid differentiation involves the activation of a number of erythroid-specific genes, most of which, including the globin genes and the erythropoietin receptor (Epo-R) gene, are, at least in part, regulated by the transcription factor GATA-1. In order to understand the relationship, if any, between expression of GATA-1, response to Epo and erythroid differentiation, we analyzed the expression of GATA-1, Epo-R and globin genes in an Epo-dependent human cell line, UT-7 Epo. The results were compared to those obtained with the parental granulocyte-macrophage colony-stimulating factor (GM-CSF)-dependent cell line, UT-7, which has a predominantly megakaryoblastic phenotype and is unable to proliferate continuously in the presence of Epo. UT-7 Epo and UT-7 expressed similar levels of GATA-1 mRNA and binding activity. The two lines also expressed comparable levels of Epo-R mRNA while the number of Epo-binding sites on UT-7 Epo cells was one-sixth the number of UT-7 cells (2400 +/- 3 vs. 13,800 +/- 300). This difference in the number of binding sites could be due to differences in cell surface (UT-7 cells are 20% smaller than the parental UT-7 cells) or in receptor turnover. By Northern analysis, UT-7 cells expressed detectable levels of beta- and gamma-globin but not alpha-globin. In comparison, UT-7 Epo cells expressed alpha-globin and higher levels of gamma-globin (5-fold) and beta-globin (from barely to clearly detectable). Globin chains (alpha, beta and gamma) were clearly detectable by affinity chromatography in UT-7 Epo but not in UT-7 cells. The frequency of the cells which expressed beta- and gamma-globin genes in the two cell populations was measured by immunofluorescence with beta- and gamma-specific antibodies. The number of gamma-positive cells and their fluorescence intensity were higher in UT-7 Epo than in UT-7 cells (0 to 17% barely positive cells and 23 to 40% clearly positive cells, respectively), indicating that the increase in globin mRNA observed in UT-7 Epo is due to both an increase of gene expression per cell and an increase in numbers of cells containing gamma-globin. The levels of GATA-1, Epo-R and globin mRNA expressed were not affected by a 24-hour incubation of either cell line with Epo, GM-CSF or interleukin-3 (IL-3).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Dependence for the proliferative response to erythropoietin on an established erythroid differentiation program in a human hematopoietic cell line, UT-7. 851 68

The interleukin-2 (IL-2) receptor (IL-2R) consists of three distinct subunits (alpha, beta, and gamma c) and regulates proliferation of T lymphocytes. Intracellular signalling results from ligand-mediated heterodimerization of the cytoplasmic domains of the beta and gamma c chains. To identify the residues of gamma c critical to this process, mutations were introduced into the cytoplasmic domain, and the effects on signalling were analyzed in the IL-2-dependent T-cell line CTLL2 and T-helper clone D10, using chimeric IL-2R chains that bind and are activated by granulocyte-macrophage colony-stimulating factor. Whereas previous studies of fibroblasts and transformed T cells have suggested that signalling by gamma c requires both membrane-proximal and C-terminal subdomains, our results for IL-2-dependent T cells demonstrate that the membrane-proximal 52 amino acids are sufficient to mediate a normal proliferative response, including induction of the proto-oncogenes c-myc and c-fos. Although gamma c is phosphorylated on tyrosine upon receptor activation and could potentially interact with downstream molecules containing SH2 domains, cytoplasmic tyrosine residues were dispensable for mitogenic signalling. However, deletion of a membrane-proximal region conserved among other cytokine receptors (cytoplasmic residues 5 to 37) or an adjacent region unique to gamma c (residues 40 to 52) abrogated functional interaction of the receptor chain with the tyrosine kinase Jak3. This correlated with a loss of all signalling events analyzed, including phosphorylation of the IL-2R beta-associated kinase Jak1, expression of c-myc and c-fos, and induction of the proliferative response. Thus, it appears in T cells that Jak3 is a critical mediator of mitogenic signaling by the gamma c chain.
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PMID:A membrane-proximal region of the interleukin-2 receptor gamma c chain sufficient for Jak kinase activation and induction of proliferation in T cells. 852 10

Dendritic cells (DC) have been shown to develop along a myeloid or lymphoid lineage of differentiation propagated from bone marrow or early thymic precursor cells with hematopoietic cytokines. In our study, we have induced growth and differentiation of DC from cord blood CD34+ cells initiated in interleukin-2 (IL-2) alone or in IL-2 + stem cell factor (SCF) + tumor necrosis factor alpha (TNF-alpha)-supplemented medium and cultured with IL-2 or IL-2 + SCF for 28-35 days. Dendritic morphology and antigenic phenotype of DC grown with IL-2 were characteristic for DC cultured in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF). Growth and differentiation of DC was followed by an increase in expression of MHC II and co-stimulating molecules CD80 and CD86. We have also shown the expression of the IL-2 receptor (IL-2R) gamma-chain in CD34+ cells after 2-3 days of culture with IL-2 alone. The co-expression of the IL-2R alpha, beta, and gamma subunits in both DC cultured with IL-2- or GM-CSF-containing cocktail of cytokines was also shown. The time curve for induction of IL-2R demonstrated low levels of subunit expression at the beginning of culture. The number of CD1a cells co-expressing CD25, CD122, and CDgamma increased to about 24-68 and to 78-95% after 21 and 28-35 days, respectively. Development of natural killer cells was shown along with DC. The proportion of CD56+ cells and cytotoxicity increased in a time-dependent manner.
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PMID:Interleukin-2-induces development of denditric cells from cord blood CD34+ cells. 958 7

Receptor activation by the haematopoietic growth factor proteins interleukin 5 (IL-5) and granulocyte-macrophage colony-stimulating factor (GM-CSF) leads to phosphorylation of JAK2 as a key trigger of signal transduction. JAB has recently been identified as a regulator of JAK2 phosphorylation and activity by binding phosphorylated JAK2 and inducing its degradation. As part of our effort to define molecular recognition networks that lead to signalling, we investigated the effect of JAB on both JAK2 phosphorylation and JAK2 interaction state that ensue upon IL-5 stimulation in recombinant 293T cells cotransfected 293T cells with IL-5R alpha, beta c and hJAK2 either with or without JAB. Without JAB, stimulation with wild-type and re-engineered single chain (sc) IL-5 induced a time-dependent phosphorylation of JAK2. In the presence of JAB cotransfection, no phospho-JAK2 was observed, and JAB was observed co-immunoprecipitated with non-phosphorylated JAK2. The time dependence of JAB co-immunoprecipitation correlated with the time dependence of JAK2 phosphorylation when JAB was absent. Since JAB has already been shown to bind JAK2 via a phosphorylated tyrosine, the current data suggest that JAB binds to phosphorylated JAK2, enhances JAK2 dephosphorylation and remains associated in a complex, with dephosphorylated JAK2, that may be a precursor leading to irreversible JAK2 degradation.
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PMID:IL-5-Induced JAB-JAK2 interaction. 1097 87

Over the past few years, evidence has emerged for the potential role of the human bronchial epithelial cell in the initiation and progress of inflammation of the airway. Thus, the aim of this study was to investigate the expression pattern of cytokines and immunomodulatory factors in the human bronchial epithelial cell. To elucidate this highly complex expression and regulation pattern, the simian virus-40 transformed human bronchial-epithelial cell line BEAS-2B was stimulated with human recombinant tumour necrosis factor (hrTNF)-alpha (10 ng x mL(-1) (specific activity, 2.86 x 10(7) U x mg(-1))) and messenger ribonucleic acid (mRNA) expression pattern was analysed by complementary deoxyribonucleic acid (cDNA) array analysis. Among 375 arrayed cDNA clones, 173 (46%) were detected in BEAS-2B cells. The levels of expression of 17 genes, including those of monocyte chemoattractant protein (MCP)-1, intercellular adhesion molecule (ICAM)-1, growth-related oncogene (GRO) alpha, beta, gamma, interleukin (IL)-7 receptor, CD70, IL-6, IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF) and regulated in activation, normal T-cell expressed and secreted (RANTES) were elevated after TNF-alpha stimulation. The differential character of 12 clones was further characterised and verified by real time polymerase chain reaction (PCR) analysis of total ribonucleic acid (RNA) isolated from BEAS-2B cells after 4 or 16 h incubation with increasing TNF-alpha concentrations (1 pg-10 ng x mL(-1)). The authors semiquantified concentration-dependent mRNA upregulation of cytokines and immunology factors identified in the array and could determine threshold values of mRNA increases at 10 pg x mL(-1)-1 ng x mL(-1) TNF-alpha by real-time PCR. For CD70 (CD27 ligand) and interleukin-7 receptor, which to the best of the author's knowledge have not yet been described in the human bronchial epithelial cell, a rapid and continuous messenger ribonucleic acid increase induced by 100 pg x mL(-1) tumour necrosis factor-alpha after only 60-90 min was shown. A potential role for these genes in the inflammatory process in the human bronchial epithelial cell is proposed.
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PMID:Tumour necrosis factor-alpha induced CD70 and interleukin-7R mRNA expression in BEAS-2B cells. 1221 69