Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P14784 (IL-2 receptor)
 3,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interleukin 6 (IL-6) signal is transduced through gp130 that associates with a complex of IL-6 and IL-6 receptor. Truncations or amino acid substitutions offe introduced in the cytoplasmic region of human gp130, and the mutant cDNAs were transfected into murine interleukin 3-dependent cells to determine amino acid residues critical for generating the IL-6-mediated growth signal. In the 277-amino acid cytoplasmic region of gp130, a 61-amino acid region proximal to the transmembrane domain was sufficient for generating the growth signal. In this region, two short segments were significantly homologous with other cytokine-receptor family members. One segment is conserved in almost all members of the family, and the other is found especially in granulocyte colony-stimulating factor receptor, interleukin 2 receptor beta chain, erythropoietin receptor, KH97 (a granulocyte/macrophage colony-stimulating factor receptor-associated molecule), and interleukin 3 receptor. gp130 molecules with mutations in either of these two segments could not transduce growth signal. Loss of signal-transducing ability of gp130 with such a mutation coincided with disappearance of IL-6-induced tyrosine phosphorylation of gp130.
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PMID:Critical cytoplasmic region of the interleukin 6 signal transducer gp130 is conserved in the cytokine receptor family. 166 92

The authors measured plasma IL-1 (interleukin-1), IL-2, IL-2 receptor (IL-2R), IL-4, IL-6, tumor necrosis factor (TNF), and granulocyte macrophage colony stimulating factor (GMCSF) in 10 stable patients during hemodialysis (HD) using new or reused polyacrylonitrile (PAN) or cuprophan (CU) dialyzers. Five HD patients with wasting syndrome, and 16 normal controls, were included. Hemodialysis patients showed a marked elevation of IL-2R. No IL-4, IL-6, or GMCSF were detected in any group. Tumor necrosis factor and IL-2 in the HD group were comparable with control values. No difference was found in the TNF levels in HD patients with and without wasting syndrome. Cytokine levels were unaffected by either new or used PAN or CU dialyzers.
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PMID:Cytokine levels during hemodialysis. 175 Dec 2

We examined the role of cytokines in the cutaneous response to the application of trinitrochlorobenzene (TNCB) in both nonsensitized and sensitized mice, i.e., in the irritant reaction (IR) and contact hypersensitivity reactions (CH). When administered immediately before challenge, anti-tumor necrosis factor (TNF) antibody abrogated the ear swelling response in CH; antibody directed against interferon gamma or antibodies to both granulocyte/macrophage colony-stimulating factor and interleukin 3 (IL-3) had a partial inhibitory effect; anti-IL-2 receptor antibody had no effect. Anti-TNF prevented the various features of the CH, as seen on histological sections, e.g., leukocyte infiltration and hemorrhages within the dermis and keratinocytes necrosis. Anti-TNF antibody also prevented the IR. The presence of TNF mRNA was evaluated on Northern blots; TNF-alpha mRNA was detectable in an untreated ear, increased after the application of TNCB in nonsensitized mice, and was highest in sensitized mice. TNF mRNA accumulation, which was evident 0.5 h after hapten application and lasted greater than 72 h, was abolished by treatment with anti-TNF antibody, thus suggesting an auto-amplification of TNF production. The cellular origin of TNF mRNA was explored by in situ hybridization; basal keratinocytes showed the highest labeling, but TNF mRNA was also detectable in cells of the dermal infiltrate. After hapten (TNCB) application at sites susceptible (the ear) or resistant (the foot pad) to CH or IR, a close correlation was observed between TNF mRNA accumulation and the intensity of the inflammatory reaction. The major role played by TNF in both the CH and the IR explains the histologically similar aspects of these reactions and the extreme variability of these reactions at various anatomical sites.
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PMID:Tumor necrosis factor is a critical mediator in hapten induced irritant and contact hypersensitivity reactions. 190 80

Malignant cells of a patient with acute leukemia expressed hematopoietic stem cell antigens such as CD34 and HLA-class II but lacked lineage specific differentiation markers. The leukemic blasts differentiated into mature T cells within 14 days in the presence of a T cell conditioned medium or with a mixture of highly purified interleukin-2 (IL-2) plus recombinant interleukin-3 (IL-3) and recombinant granulocyte/macrophage colony-stimulating factor (GM-CSF). Phenotypically, the maturing cells acquired the T cell-specific differentiation antigens CD2, CD3, and CD8, whereas immature differentiation antigens such as CD34 and Leu19 as well as HLA-class II and the IL-2 receptor CD25 were concomitantly down-regulated within 14 days of in vitro culture. This in vitro maturation involved two to three synchronized cell divisions. Beyond 10 days of culture the leukemic cells produced mRNA specific for the T cell receptor beta and alpha chain, but at no time transcription of T cell receptor gamma chain-specific message was detectable. To our knowledge, these data represent the first in vitro model demonstrating the differentiation of phenotypically mature T cells from immature leukemic cells induced by the combined activities of IL-2 plus IL-3 and GM-CSF.
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PMID:Generation of mature CD3+ and T cell receptor (TCR) + T cells from a leukemic analogue of the putative human stem cell by T cell conditioned medium containing IL-3, IL-2, and GM-CSF. 245 58

HTLV-I infection of peripheral mature T cells appears to induce the expression of cellular genes including those of some cytokines and their receptors. We examined the expression of interleukin-1 alpha (IL-1 alpha), IL-1 beta, IL-2, IL-3, IL-4 and granulocyte/macrophage colony-stimulating factor (GM-CSF) at the mRNA level in fresh leukemic cells from 20 adult T cell leukemia patients to see whether there is any association between cytokine expression and HTLV-I expression and between their expression and clinical manifestations such as hypercalcemia or neutrophilia. IL-1 alpha, IL-1 beta and IL-3 expression was observed in 3, 7 and 1 of 20 cases examined, respectively. However, there seemed to be no association between IL-1 expression and clinical manifestations. IL-2, IL-4 and GM-CSF mRNA expression was not detected. HTLV-I viral RNA expression was detected only in one case in which IL-3 mRNA was expressed in both peripheral blood and lymph node cells and a relatively high proportion of leukemic cells expressed IL-2 receptor (p55, Tac). Thus, in the present study we could not find any correlation between cytokine expression and HTLV-I expression in peripheral blood fresh leukemic cells except in one unusual case.
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PMID:Expression of cytokine mRNA in leukemic cells from adult T cell leukemia patients. 250 74

CD3+ WT31- T cells were sorted from peripheral blood of a normal healthy donor by a FACS IV and cloned by limiting dilution in the presence of a phorbol ester (tetradecanoyl phorbol acetate, TPA), calcium ionophore (ionomycin, Io), interleukin-2 (IL-2), allogeneic cells, and phytohemagglutinin (PHA). One of the derived clones, 290-2, was investigated in detail. 290-2 mediated strong natural killer (NK) but not lymphokine-activated killer (LAK) activity. It proliferated in the presence of IL-2 but not IL-4. It carried the surface phenotype CD3+ WT31- CD4weak+ CD8-, CD16-, and Leu 19+. Expression of CD4 was heterogeneous within the clone, since two of three subclones were also CD4weak+ but one was CD4-. NK activity was blocked by monoclonal antibody (moAb) to CD1 1a (LFA1), but not by monoclonal antibody (moAb) to either CD3 or CD4. Northern blotting revealed T-cell receptor (TCR-gamma) but not alpha- or full-length beta-chain mRNA. 290-2 proliferated autonomously when stimulated with a combination of TPA +Io, with PHA or CD3 moAb and autologous B-cell lines (B-LCL) (and this was inhibited by an anti-IL-2 receptor moAb), but not to allogeneic B-LCL or any of the other stimulating agents alone. Unexpectedly, the TPA + Io stimulus which resulted in maximal proliferative responses did not trigger interferon-gamma or granulocyte/macrophage colony-stimulating factor production, although both lymphokines were secreted in the presence of B-LCL + TPA + Io. Proliferative responses were not enhanced by the presence of B-LCL. Thus, activation signals sufficient for autocrine proliferative responses were insufficient for secretion of other lymphokines. Such clones will provide valuable reagents for investigating the biology of the TCR-gamma+ T cell.
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PMID:Different signals for stimulation of proliferation and lymphokine secretion by a CD3+ WT31- cloned cytotoxic lymphocyte. 296 87

Interleukin 15 (IL-15) is a novel cytokine that has recently been cloned and expressed. Whereas it has no sequence homology with IL-2, IL-15 interacts with components of the IL-2 receptor (IL-2R). In the present study we performed a functional analysis of recombinant IL-15 on phenotypically and functionally distinct populations of highly purified human natural killer (NK) cells. The CD56bright subset of human NK cells constitutively expresses the high affinity IL-2R and exhibits a brisk proliferative response after the binding of picomolar amounts of IL-2. Using a proliferation assay, IL-15 demonstrated a very steep dose-response curve that was distinct from the dose-response curve for IL-2. The proliferative effects of IL-15 could be abrogated by anti-IL-2R beta (p75), but not by anti-IL-2R alpha (p55). The proliferative effects of IL-2 on CD56bright NK cells could be inhibited by both antibodies. CD56dim NK cells express the intermediate affinity IL-2R in the absence of the high affinity IL-2R. Activation of CD56dim NK cells by IL-15 was similar to that of IL-2 as measured by enhanced NK cytotoxic activity, antibody-dependent cellular cytotoxicity, and NK cell production of interferon gamma, tumor necrosis factor alpha, and granulocyte/macrophage colony-stimulating factor. The IL-15-enhanced NK cytotoxic activity could be completely blocked by anti-IL-2R beta monoclonal antibody. The binding of radiolabeled IL-2 and IL-15 to CD56dim NK cells was inhibited in the presence of anti-IL-2R beta. Scatchard analysis of radiolabeled IL-15 and IL-2 binding to NK-enriched human lymphocytes revealed the presence of high and intermediate affinity receptors for both ligands. IL-15 is a ligand that activates human NK cells through components of the IL-2R in a pattern that is similar but not identical to that of IL-2. Unlike IL-2, IL-15 is produced by activated monocytes/macrophages. The discovery of IL-15 may increase our understanding of how monocytes/macrophages participate in the regulation of NK cell function.
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PMID:Interleukin (IL) 15 is a novel cytokine that activates human natural killer cells via components of the IL-2 receptor. 752 71

Cytokine is a generic term of biologically active molecules which are mainly produced by the immune-competent cells and regulate the immune response, inflammation and hematopoiesis. This includes interleukins (IL), colony-stimulating factors (CSF), interferons (IFN), tumor necrosis factors (TNF) and so on. These cytokines are glycoproteins with a molecular weight of 20,000-40,000 kD and work at very low concentrations of pM order. ILs and CSFs transduce their signal via specific cell-membrane receptors which usually consist of at least two subunits and belong to a newly identified superfamily of cytokine receptors. Characterization of cytokine/receptor system has had a considerable impact on many clinical fields including pathophysiology of diseases and therapy. For example, IL-4 and IL-5 has been revealed to play essential roles in IgE production in allergic diseases and eosinophilia in a hypereosinophilic syndrome, respectively. Receptor abnormality has also been proven to cause diseases; patients for X-linked severe combined immunodeficiency (X-SCID) have a specific defect in the gamma chain of the IL-2 receptor which is critical for thymic maturation of T cells. EPO, G-CSF, M-CSF, IFN, and IL-2 are already commercially available for therapeutic use. IL-1, IL-3, IL-6, and TNF may also be useful for mycosis fungoides, aplastic anemia, thrombocytopenia, and malignant melanoma, respectively. On the other hand, it is possible to modulate the immune response by using the monoclonal antibody directed to the cytokine receptor.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Cytokine and disease]. 752 45

The Janus family of kinases (JAKs) has been shown to be involved in the signal transduction of a number of cytokine receptors. Recently, we have cloned a novel JAK family member, JAK3, that is expressed in natural killer and activated T cells and is coupled functionally and physically to the interleukin 2 (IL-2) receptor in these cells. Here we report that JAK3 was expressed at low but detectable levels in human monocytes. In contrast, JAK3 expression was strongly induced during activation by interferon gamma (IFN-gamma) or lipopolysaccharide. Moreover, JAK3 became tyrosine phosphorylated in response to IL-2, IL-4, and IL-7 but not response to IFN-gamma or granulocyte/macrophage colony-stimulating factor. Together, these findings suggest that JAK3 is functionally important in activated monocytes and cells of the myeloid lineage and is involved in signaling responses of cytokines that use the common gamma-chain of the IL-2 receptor.
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PMID:Regulation of JAK3 expression in human monocytes: phosphorylation in response to interleukins 2, 4, and 7. 753 38

Blood levels of inhaled corticosteroids are significantly lower than those measured in the lung, but their concentration could still have anti-inflammatory effects. To determine whether budesonide, at concentrations similar to those obtained in blood after drug inhalation (10(-9) M), could downregulate the allergen-induced activation of mononuclear cells, we studied 21 atopic patients, sensitized to Dermatophagoides pteronyssinus (Der p). On blood mononuclear cells, isolated from these patients, incubated with Der p allergen extract and with or without budesonide, we evaluated: 1) the proliferative response of T cells; 2) the expression of two surface activation markers, the HLA-DR antigens and the interleukin (IL)-2 receptors; and 3) the release of cytokines known to modulate the allergic processes. Allergen-induced T-cell proliferation was associated with increased HLA-DR antigen and IL-2 receptor expression (P < 0.001), and with increased release of IL-2, interferon-gamma (IFN-gamma), IL-1 beta, tumor necrosis factor-alpha (TNF-alpha), and granulocyte/macrophage colony-stimulating factor (GM-CSF). The addition of budesonide at the beginning of the cell cultures induced a dose-dependent inhibition of T-cell proliferation, still significant (P < 0.05) at the lowest concentrations tested (10(-9) and 10(-10) M). A significant inhibitory effect on T-cell proliferation was also present when budesonide (10(-9) M) was added to the cell cultures 3 or 5 days after the beginning of the cell cultures.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of "systemic" budesonide concentrations on in vitro allergen-induced activation of blood mononuclear cells isolated from asthmatic patients. 757 28


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