UNIPROT:P14784 - FACTA Search

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Query: UNIPROT:P14784 (IL-2 receptor)
3,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fresh lymph-borne (veiled) dendritic cells (L-DC) in the rat are almost totally negative for the interleukin-2 (IL-2) receptor detected by the monoclonal antibody (mAb) MRC OX39. After 16 hr culture more than 90% of L-DC are OX39 positive, and increased levels of expression can be seen within 5 hr culture. In cultures of L-DC and allogeneic lymphocytes. L-DC appear to express the IL-2 receptor more rapidly than lymphocytes. The intensity of labelling of L-DC is variable but maximal levels are similar to those seen on lymphoblasts. Culture in the presence of concanavalin A (Con A)-stimulated spleen cell supernatants or recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) results in a more rapid and intense expression of the IL-2 receptor by L-DC. L-DC cultured following rigorous T-cell depletion, or derived from athymic rats also express the IL-2 receptor after culture with GM-CSF. Cultured, but not fresh, L-DC bind iodinated recombinant IL-2 in a dose-dependent manner and binding is inhibited by excess unlabelled ligand. The amount of IL-2 bound varies but maximal amounts are similar to those bound by lymphoblasts. Following intravenous endotoxin injection, a large proportion of freshly collected L-DC express the IL-2 receptor and the number of L-DC released into the lymph is increased. An antibody to the IL-2 receptor which blocks an allogeneic MLR has no effect on a xenogeneic MLR using rat L-DC as stimulators and mouse lymphocytes as responders.
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PMID:Properties of lymph-borne (veiled) dendritic cells in culture. II. Expression of the IL-2 receptor: role of GM-CSF. 268 Sep 7

Three lines of transgenic mice carrying the human T-cell lymphotropic virus type 1 tax gene have previously been reported to develop neurofibromas composed of perineural fibroblasts (S. H. Hinrichs, M. Nerenberg, R. K. Reynolds, G. Khoury, and G. Jay, Science 237:1340-1343, 1987; M. Nerenberg, S. H. Hinrichs, R. K. Reynolds, G. Khoury, and G. Jay, Science 237:1324-1329, 1987). Tumors from these mice and tumor cell lines derived from them expressed high levels of tax RNA and protein. They also expressed high levels of the granulocyte-macrophage colony-stimulating factor (GM-CSF) gene as measured by proliferative responses of FD-CP1 target cells using conditioned media from tumor cells and by Northern (RNA) blot analysis of RNA from tumors and tumor cell lines. Although other tissues, such as salivary glands and muscles, in the transgenic mice also expressed high levels of tax, they did not express the gene for GM-CSF. This indicates that tissue-specific cellular factors, in addition to tax, are required for GM-CSF gene expression. Systemic effects of excessive GM-CSF production were demonstrated by infiltration of polymorphonuclear leukocytes into tumor tissues which are not necrotic, by peripheral granulocytosis, and by splenomegaly resulting from myeloid hyperplasia. The interleukin-2 (IL-2) receptor was also found to be expressed by the tumors and tumor cell lines as measured by IL-2-binding and cross-linking studies. This is the first demonstration that the IL-2 receptor can be activated by tax in a nonlymphoid cell type. These in vivo findings are consistent with other reports which have demonstrated in vitro cis-regulatory elements within the 5'-flanking regions of the genes for GM-CSF and the IL-2 receptor which are responsive to trans activation by the tax gene.
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PMID:trans activation of granulocyte-macrophage colony-stimulating factor and the interleukin-2 receptor in transgenic mice carrying the human T-lymphotropic virus type 1 tax gene. 268 63

Interleukin-2 (IL-2)-dependent large granular lymphocytes (LGL) with a distinctive surface phenotype were generated from histologically normal duodenal biopsy tissues. Immunoperoxidase staining of the mucosa with an anti-CD56 monoclonal antibody revealed LGL localized in the lamina propria rather than in the epithelium. Light and electron microscopy demonstrated azurophilic and electron-dense cytoplasmic granules. Flow cytometry analysis revealed that these cells express CD45, CD56, CD2, CD7, CD11a, CD18, CD69 and the intermediate affinity (p70) IL-2 receptor (IL-2R) but not CD57, CD16, CD3, CD4, CD5, CD8, CD45RA, CD25, or the high affinity p55 IL-2R. The LGL proliferated when cultured in the presence of human rIL-2 but not in the presence of human rIL-4. Functional studies demonstrated that the LGL had strong cytotoxicity against natural killer (NK) target cells, K562, but not NK-resistant targets such as Colo 205, Melanoma and Epstein-Barr virus (EBV)-transformed B-cell lines. The LGL expressed genes for IL-5, IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF) and tumour necrosis factor-alpha (TNF-alpha) and the corresponding cytokines were detected in culture supernatant. These results provide evidence for an important role of gut mucosal LGL in the induction and regulation of inflammation and immunity in the gut.
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PMID:Morphological, phenotypic and functional characteristics of a pure population of CD56+ CD16- CD3- large granular lymphocytes generated from human duodenal mucosa. 769 28

Serum levels of 13 different cytokines and receptors were measured serially in 78 patients with aggressive non-Hodgkin's lymphoma (NHL) treated by 4 cycles of an intensive multi-agent chemotherapy regimen. Recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) was administered subcutaneously in 36 of these patients from day + 5 to day + 18 after each chemotherapy. Statistically significantly higher pretreatment levels of interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), the soluble IL-2 receptor (sIL-2r), the soluble transferrin receptor (sTf-r), and neopterin, were observed in NHL patients as compared to controls (p < 0.001 for all molecules). sIL-2r and sTf-r levels correlated with tumor burden (p < 0.001 and p = 0.003, respectively) whereas IL-6 was higher in patients presenting B symptoms (p < 0.001). Cytokine levels progressively declined to normal ranges in responding patients, while they remained elevated in non-responders. Relapsed patients also presented increased concentrations of several molecules. During the administration of GM-CSF, we observed the drastic increase of sIL-2r, while lower elevations were recorded for a number of cytokines, including IL-8, tumor necrosis factor-alpha, interleukin-1 beta, IL-6, and IL-2. However, upon completion of the induction treatment, cytokine/receptor levels were comparable among individuals with the same type of response, whether or not they had received GM-CSF. No single parameter was found to be of prognostic significance, but the combination of elevated IL-10 and of sIL-2r greater than 3000 U/ml selected a subgroup of 7 patients who failed induction treatment (p = 0.002). These results demonstrate that cytokine and soluble receptor measurements can provide valuable informations for a better management of NHL, in terms both of markers to monitor disease activity and of prognostic indicators.
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PMID:Clinical implications of cytokine and soluble receptor measurements in patients with newly-diagnosed aggressive non-Hodgkin's lymphoma. 785 83

The immunomodulator ammonium trichloro(dioxyethylene-0-0')tellurate (AS101) has previously been found by us to have radioprotective properties when injected into mice before sublethal and lethal doses of irradiation. AS101 also was found to protect mice from hematopoietic damage caused by various chemotherapeutic drugs. Based on these findings, phase II clinical trials with cancer patients treated with AS101, in combination with chemotherapy, are currently underway. In the present study, we wanted to assess the role of several cytokines in the radioprotection conferred by AS101. We show that the administration of neutralizing antibodies against interleukin-1 (IL-1) receptor, IL-6 receptor, IL-6, tumor necrosis factor (TNF), or stem cell factor (SCF) completely abrogates the ability of AS101 to increase the survival of lethally irradiated mice. Moreover, the injection of each of these antibodies reduces the ability of AS101 to increase the number of BM, spleen cells, and the number of circulating neutrophils, lymphocytes, and platelets in irradiated mice. In addition, these antibodies abrogate the enhancing effect of AS101 on the secretion of IL-3, IL-6, and granulocyte-macrophage colony-stimulating factor, all of which decrease significantly in sublethally irradiated mice. By contrast, the injection of anti-IL-2 receptor antibody or control Igs to AS101-treated mice does not interfere with the radioprotective effects of the compound. These results suggest a role for IL-1, IL-6, TNF alpha, and SCF in the radioprotective effect of AS101. Because cytokine toxicity remains a significant concern, the clinical application of AS101, which has no toxicity, is particularly valuable.
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PMID:Role of endogenous cytokines secretion in radioprotection conferred by the immunomodulator ammonium trichloro(dioxyethylene-0-0')tellurate. 788 74

Co-stimulation of highly purified peripheral T lymphocytes from healthy blood donors with the adhesion molecules CD2 and CD28 in association with recombinant interleukin-7 (rIL-7) induced T-cell proliferation, multiple cytokine secretion and IL-2 receptivity. We demonstrated that rIL-7 is as potent as rIL-2 in inducing the proliferation of unseparated, CD4+ and CD8+ T cells. In contrast to low or undetectable levels of IL-1 alpha, IL-6 and IL-2, high levels of tumour necrosis factor-alpha (TNF-alpha), IL-4 and granulocyte-macrophage colony-stimulating factor (GM-CSF) were secreted. Experiments using blocking antibodies suggested a direct mechanism for rIL-7 co-stimulatory effect, although induction of the CD25/IL-2 receptor alpha-chain (CD25/IL-2R alpha) was observed. Monoclonal antibodies (mAb) against the adhesion molecules CD2 and CD28 are likely to mimic the interaction with their respective physiological ligands [lymphocyte function-associated antigen-3 (LFA-3)/CD58, CD59 and CD48 for CD2, B7/BB1 for CD28]. Taken together, these in vitro data suggest that IL-7 could participate in paracrine interactions between T lymphocytes and thymic stromal cells or dendritic cells, via its potent co-stimulatory activity with CD2 and CD28 adhesion molecules.
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PMID:Interleukin-7 is a potent co-stimulus of the adhesion pathway involving CD2 and CD28 molecules. 790 90

In addition to the mobilization of neutrophils and monocytes, granulocyte-macrophage colony-stimulating factor (GM-CSF) also mobilizes lymphocytes into peripheral blood. We examined the ability of GM-CSF to induce the proliferation of purified human T cells (CD3+ CD4+ CD56- CD16- B1- MO2-) in two major aspects: (1) the mechanisms of GM-CSF interaction with interleukin-2 (IL-2) causing T-cell proliferation, and (2) the intracellular signals transmitted by GM-CSF in T lymphocytes. We observed that concentrations of GM-CSF between 0.01 ng/mL and 10 ng/mL had a synergistic effect with concentrations of IL-2 between 1 U/mL and 10 U/mL in stimulating T-cell proliferation. This effect of GM-CSF was maximal when it was added at the start of the culture. In situ hybridization showed the presence of mRNA for GM-CSF receptors in T cells. Further analysis showed that GM-CSF induced the expression of IL-2 receptor (IL-2R) on the surface of T lymphocytes. These events coincide with the ability of GM-CSF to increase the intracellular levels of both cyclic 3',5'-adenosine monophosphate (cAMP) and cyclic 3',5'-guanosine monophosphate (cGMP) in T cells, to increase the binding of (gamma-35S) GTP to T-cell membranes, and to enhance GTPase activity as determined by increased hydrolysis of 32P-GTP. IL-2 also induced IL-2R expression, cyclic nucleotide secretion, and G-protein activation. However, the presence of IL-2 reduced GM-CSF induction of these activities. Addition of antibodies to the alpha and beta subunits of IL-2R permitted the activation of G protein by GM-CSF even when IL-2 was present. Furthermore, GTP binding and GTPase activity induced by GM-CSF or IL-2 were inhibited by the addition of cholera toxin (CT), but not pertussis toxin (PT). Cumulatively, these results suggest that in T lymphocytes, receptors for GM-CSF or IL-2 may be coupled to the same CT-sensitive G protein, although other possibilities may exist. The role that G proteins play in mediating the intracellular signaling pathways induced by GM-CSF or IL-2 in human T cells is supported by adenosine diphosphate-ribosylation of a 44-kD or a 39-kD G protein in T-cell membranes by CT and PT, respectively.
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PMID:Priming effects of granulocyte-macrophage colony-stimulating factor are coupled to cholera toxin-sensitive guanine nucleotide binding protein in human T lymphocytes. 811 33

Adult T cell leukemia-derived factor (ADF), originally defined as an IL-2 receptor alpha-chain (IL-2R alpha)/p55 (Tac) inducer, is a human thioredoxin homologue and has many cytokine-like activities. In this study, we examined the regulatory effect of ADF on eosinophil migration using human eosinophils and an eosinophilic subline of HL-60 human promyelocytic leukemia cells, YY-1. rADF induced migration of eosinophils from patients with hypereosinophilia, although rADF exhibited little activity on eosinophils from healthy donors. When human eosinophils were incubated with rADF (0.1-10 micrograms/ml) at 37 degrees C for 24 h, both chemotactic and chemokinetic activity of the complement anaphylatoxin peptide C5a on eosinophil migration was markedly enhanced in a dose-dependent manner. Similarly, this enhancing effect of rADF was observed in the migration assay using YY-1 cells. In contrast, rADF showed no modulation of migratory behavior of human eosinophils and YY-1 cells by IL-3, IL-5, nor granulocyte-macrophage colony-stimulating factor. Scatchard analysis of C5a receptors on YY-1 cells using 125I-C5a showed that rADF modulated neither the density nor the affinity of the cell membrane significantly. Furthermore, mutant ADF (mADF), which had no reducing activity, had no enhancing effect on C5a-induced eosinophil migration. These results indicate a possible involvement of ADF in the recruitment of eosinophils through redox regulation by a dithiol reductase activity.
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PMID:Regulation of eosinophil migration by adult T cell leukemia-derived factor. 822 51

The product of the c-raf-1 proto-oncogene, Raf-1, is known to encode a 74-kDa ubiquitously expressed cytoplasmic serine/threonine kinase. Various growth factors such as epidermal growth factor, acidic fibroblast growth factor, platelet-derived growth factor, insulin, granulocyte-macrophage colony-stimulating factor, interleukin (IL)-2, IL-3 and erythropoietin have been shown to induce phosphorylation of Raf-1, thereby activating Raf-1 kinase. Raf-1 is, thus, believed to play a role in coupling growth factor receptors to proliferation. We have examined the role of Raf-1 in the mitogenic response of human peripheral blood-derived IL-2 receptor expressing T cells to human recombinant IL-2 employing c-raf antisense (AS) oligodeoxyribonucleotide. Uptake studies of oligonucleotides indicated that incorporation of oligomers was maximal at 4 h and oligodeoxynucleotides remained stable in these cells for up to 24 h. Treatment of T cells with the AS oligodeoxyribonucleotide in intracellular duplex formation followed by efficient translation blockade of c-raf-1. In contrast, sense (S) and nonsense (NS) oligodeoxynucleotides failed to form intracellular duplexes and did not interfere with translation of c-raf-1, suggesting specific elimination of c-raf-1 by the AS oligomer. Proliferation of T cells ([3H]thymidine incorporation) following exposure to IL-2 was substantially reduced when the c-raf-1 AS oligodeoxyribonucleotide was added to cultures, while the mitogenic response to this factor remained almost unaffected in the presence of S and NS oligodeoxyribonucleotides.
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PMID:The mitogenic response of T cells to interleukin-2 requires Raf-1. 825 28

Human interleukin 2 (IL-2) is a member of the class of crucial regulators of lymphocyte proliferation. The action of IL-2 is known to be mediated through binding to a specific IL-2 receptor (IL-2R) which comprises at least two distinct proteins: IL-2R alpha (p55) and IL-2R beta (p70-75). However, the expression and function of IL-2R are largely unknown in acute myeloblastic leukemia cells. In a human granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-3, or stem cell factor-dependent myeloid leukemia cell line (M07E), IL-2 was found to stimulate proliferation in a dose-dependent manner and to augment GM-CSF- and stem cell factor-induced proliferation of M07E cells. The expression of IL-2R beta on M07E cells was detectable with 125I-IL-2 binding and affinity cross-linking analyses and with a monoclonal antibody against IL-2R beta, Mik-beta 1. Although the expression of IL-2R beta was not down-regulated but somewhat up-regulated by treatment with GM-CSF in both mRNA and protein levels, GM-CSF was found to compete (75%) with radiolabeled IL-2 for binding to IL-2R on M07E cells, whereas no competition of GM-CSF binding was observed with IL-2 even at a 400-fold molar excess. These results suggest that IL-2R may be functionally expressed in some cases of acute myeloblastic leukemia cells and raise the possibility that IL-2 may have some effects on human myelopoiesis.
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PMID:Functional expression of interleukin 2 receptor in a human factor-dependent megakaryoblastic leukemia cell line: evidence that granulocyte-macrophage colony-stimulating factor inhibits interleukin 2 binding to its receptor. 842 2

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