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)

The primary interleukin-4 (IL-4) receptor complex on monocytes (type I IL-4 receptor) includes the 140-kDa alpha chain (IL-4R alpha) and the IL-2 receptor gamma chain, gamma(c), which heterodimerize for intracellular signaling, resulting in suppression of lipopolysaccharide (LPS)-inducible inflammatory mediator production. The activity of IL-13 on human monocytes is very similar to that of IL-4 because the predominant signaling chain (IL-4R alpha) is common to both receptors. In fact, IL-4R alpha with IL-13R alpha1 is designated both as an IL-13 receptor and the type II IL-4 receptor. When the anti-inflammatory activities of IL-4 and IL-13 were investigated on synovial fluid macrophages and compared with the responses by monocytes isolated from the patients at the same time as joint drainage, the response profiles differed with some responses similar in the two cell populations, others reduced on the inflammatory cells. Similar differences were recorded in the response profiles to IL-4 and IL-13 by monocytes and monocytes cultured for 7 days in macrophage colony-stimulating factor (M-CSF) or granulocyte-macrophage CSF (GM-CSF) (monocyte-derived macrophages, MDMac). MDMac have reduced gamma(c) mRNA levels and reduced expression of the functional 64-kDa gamma(c). There was a similar loss of IL-13R alpha1 mRNA on monocyte differentiation. In turn, there was a significant reduction in the ability of IL-4 and IL-13 to activate STAT6. These findings suggest that different functional responses to IL-4 and IL-13 by human monocytes and macrophages may result from reduced expression of gamma(c) and IL-13R alpha1.
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PMID:Differential responses of human monocytes and macrophages to IL-4 and IL-13. 1053 11

Interleukin-4 (IL-4) regulates the expression of the 55-kDa alpha-subunit (CD25) of the IL-2 receptor complex in human B lymphocytes. This report suggests that the cAMP/protein kinase A (PKA) component of the IL-4 receptor signalling programme in human tonsillar B cells has a functionally important role in regulating expression of the CD25 gene by attenuating activity of a protein binding to a potent negative regulatory element (NRE) in the CD25 promoter; this effect can be mimicked by agents that elevate cAMP and blocked by inhibitors of PKA but not protein kinase C (PKC). In a B-cell line that fails to elevate cAMP, attenuate NRE-binding protein (NRE-BP) activity or express CD25 following IL-4 treatment, stimulation of cAMP accumulation by forskolin facilitates IL-4-mediated induction of both the endogenous gene and an exogenous reporter gene under the control of a minimal promoter/enhancer fragment of the CD25 gene.
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PMID:A functional role for interleukin (IL)-4-driven cyclic amp accumulation in human b lymphocytes. 1084 54

We have identified a type I cytokine receptor, which we have termed novel interleukin receptor (NILR), that is most related to the IL-2 receptor beta chain (IL-2Rbeta) and physically adjacent to the IL-4 receptor alpha chain gene on chromosome 16. NILR mRNA is most highly expressed in thymus and spleen, and is induced by phytohemagglutinin in human peripheral blood mononuclear cells. NILR protein was detected on human T cell lymphotropic virus type I-transformed T cell lines, Raji B cells, and YT natural killer-like cells. Artificial homodimerization of the NILR cytoplasmic domain confers proliferation to Ba/F3 murine pro-B cells but not to 32D myeloid progenitor cells or CTLL-2 murine helper T cells. In these latter cells, heterodimerization of IL-2Rbeta and the common cytokine receptor gamma chain (gamma(c)) cytoplasmic domains allows potent proliferation, whereas such heterodimerization of NILR with gamma(c) does not. This finding suggests that NILR has signaling potential but that a full understanding of its signaling partner(s) is not yet clear. Like IL-2Rbeta, NILR associates with Jak1 and mediates Stat5 activation.
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PMID:Cloning of a type I cytokine receptor most related to the IL-2 receptor beta chain. 1101 59

Recent studies have defined several phenotypic and molecular changes associated with the maturation of naive human B cells within the milieu of germinal centers. Although naive B cells serve as natural precursors to germinal center (GC)/memory (M) subpopulations, little is known about the physiological requirements for the survival of the naive B cell pool in the absence of cell-cell contact or Ag-mediated activation. Because IL-4 induces expression of several membrane receptors such as CD23 which are uniquely present on resting human naive B lymphocytes, we hypothesized that these cells might be intrinsically programmed to respond to IL-4 in the absence of cell division. Using buoyant density-dependent isolation and further enrichment by negative/positive selection of human naive and GC/M subpopulations, we characterized cytokine receptor moieties on these cells and analyzed their survival and growth in the presence of IL-4 or IL-10. Resting naive B cells expressed significantly higher IL-4 receptor alpha-chain on their cell surface than the combined GC/M subpopulation. The IL-10 receptor and the IL-2 receptor gammac chain were almost equally expressed on both subpopulations. When cultured in vitro, the addition of IL-4, but not IL-10, protected naive B cells from apoptosis in the absence of activation and growth. However, IL-4 exerted no such effect on resting GC/M B cells. These data support the hypothesis that IL-4 plays a pivotal role in the survival and maintenance of resting human naive B cells.
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PMID:Novel diversity in IL-4-mediated responses in resting human naive B cells versus germinal center/memory B cells. 1106 12

The biologic activities of interleukin (IL)-13 and IL-4 often overlap, and evidence supports their importance in atopic disease and airways hyperresponsiveness. Here, their capacity to release eosinophil-activating cytokines was examined in cultured human airway smooth muscle. IL-13 and IL-4 induced selective release of eotaxin with no effect on granulocyte-macrophage colony-stimulating factor, regulated upon activation, normal T-cell expressed and secreted (RANTES), or IL-8. A profound synergistic increase in eotaxin release occurred when IL-13 or IL-4 was combined with IL-1beta that was abrogated by a neutralizing antibody to the IL-4 receptor alpha (IL-4Ralpha)-chain but not to the IL-2 receptor gamma (IL-2Rgamma)-chain. Expression of cell surface IL-4 receptors and IL-4Ralpha in lysates was constitutive and unchanged by treatment with IL-13 or IL-4 alone or in combination with IL-1beta. Activation of IL-4Ralpha by IL-13 or IL-4 induced signal transducer and activation of transcription-6 (STAT6), p42/ p44 ERK, p38, and to a lesser extent, SAPK/JNK mitogen-activated protein kinase phosphorylation. STAT6 and MAP kinase activation by IL-13 or IL-4 was not further potentiated after combined stimulation with IL-1beta. However, eotaxin release induced by IL-13 or IL-4 alone, and in combination with IL-1beta, was prevented by the MEK inhibitor U 0126 and by the p38 inhibitor SB 202190. Collectively, the data suggest that selective eotaxin release induced either by IL-13 and IL-4 or when combined with IL-1beta is mediated by a constitutive cell surface IL-4Ralpha and the activation of multiple intracellular pathways.
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PMID:Selective induction of eotaxin release by interleukin-13 or interleukin-4 in human airway smooth muscle cells is synergistic with interleukin-1beta and is mediated by the interleukin-4 receptor alpha-chain. 1195 62

In order to investigate the mechanisms by which cytokines and tumor promoters stimulate cell growth, the expression of genes implicated in the regulation of cellular proliferation were examined in an interleukin-3 (IL-3) dependent hematopoietic cell line. Upon stimulation of factor-deprived cells with IL-3, mRNA transcripts encoding the immediate-early genes: c-myc, jun-B, krox-20, beta-actin, and the cytokine genes: IL-4 and IL-6 were detected within 1 h. In contrast mRNA transcripts encoding the delayed-early genes: ornithine decarboxylase, p53, the IL-2 receptor-alpha, IL-4 receptor, and the T cell receptor c-gamma chains were observed at highest levels later. The tumor promoter, phorbol 12-myristate 13-acetate also stimulated the expression of many immediate-early genes, however, c-myc and the delayed-early genes were only detected when IL-3 was present. We conclude that cytokines and tumor promoters have distinct effects on proto-oncogene expression in hematopoietic cells which may affect the ability of these agents to promote cellular growth versus differentiation.
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PMID:Differential-effects of tumor promoters and cytokines on protooncogene expression in a hematopoietic cytokine-dependent cell-line. 2160 54

The cytokines interleukin (IL)-2 and IL-4 are important regulators of the adaptive immune response, due in part to their effects on clonal expansion and differentiation of T cells. When IL-2 and IL-4 are administered together, both antagonistic and synergistic effects have been reported, but little is known in general concerning the mechanisms underlying such combinatorial effects. We found evidence for both effects in the proliferation responses of the IL-2 and IL-4 responsive T cell line, HT-2; IL-4 delays the onset of cell growth yet ultimately allows a higher cell density to be achieved in static culture. At the level of signal transduction pathways, we found that IL-4 partially inhibits IL-2 receptor-mediated pathways (PI3K/Akt, Ras/Erk, and STAT5a/b) and does not prolong their transient kinetics. This mode of antagonism, but not the effects on cell proliferation, is overcome at higher concentrations of IL-2 that are sufficient to saturate the signaling responses. By comparison, IL-4-stimulated activation of STAT6 is unaffected by IL-2 and shows sustained kinetics, and we speculate that this or another IL-4 receptor-specific pathway is responsible for the effects of IL-4 on IL-2-stimulated proliferation. A possibly related observation is that IL-4 induces a dramatic cell adhesion phenotype.
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PMID:Combinatorial Signal Transduction Responses Mediated by Interleukin-2 and -4 Receptors in a Helper TH2 Cell Line. 2425 93


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