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)

Histological observations have demonstrated the presence of T lymphocytes in atherosclerotic plaques, often in close association with vascular smooth muscle cells (VSMC). We have examined the interaction occurring between cloned murine VSMC and histocompatibility-matched, antigen-specific Th1 and Th2 cell lines. Incubation of either Th1 or Th2 cells with antigen-pulsed VSMC resulted in the formation of T cell-VSMC conjugates accompanied by morphological changes in both cell types. This interaction resulted in an antigen-dependent activation of IL-2 receptor expression by the Th cells, demonstrating the ability of cloned VSMC to process and present antigen through the exogenous pathway. However, although the T cells were activated to express IL-2 receptors by antigen-pulsed VSMC, they were unable to progress through cell cycle. The secretion of an inhibitory mediator by VSMC was suggested by the observations that (1) fixation of the VSMC's eliminated the inhibitory signal and (2) the supernatants of IFN gamma-primed VSMC displayed similar inhibitory activity. The inhibitory effect could not be abrogated with indomethacin or an inhibitor of the generation of reactive nitrogen intermediates, indicating that prostaglandin synthesis and/or nitric oxide production are not solely responsible for the inhibition of proliferation. Flow cytometric cell cycle analysis revealed that VSMC delivered signals resulting in a late G1 blockade of T cell cycle progression. Mitogen responses of purified primary T cells are also dramatically inhibited by IFN gamma-treated VSMC, despite significant IL-2 production. Our data depict a complex and intimate T cell-VSMC interaction and suggest that mutual activation events may occur.
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PMID:T cell--vascular smooth muscle cell interactions: antigen-specific activation and cell cycle blockade of T helper clones by cloned vascular smooth muscle cells. 773 69

Interleukin-2 (IL-2)-like immunoreactivity and IL-2 receptor immunoreactivity have been reported in different brain regions, under normal and pathophysiological conditions. IL-2 stimulates hypothalamic corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) release and that of pituitary adrenocorticotropin. The amygdala, known to contain high levels of CRF, is involved in stress-related reactions, including regulation of the hypothalamo-pituitary-adrenal axis. IL-2 will release AVP from both the hypothalamus and the amygdala, which further supports a role for cytokine effects in the amygdala in neuroimmune interactions. In the present study, we compared the effects of IL-2, acetylcholine and norepinephrine on the in vitro release of CRF from the amygdala or hypothalamus. In addition, we used these release systems to evaluate the possible involvement of nitric oxide (NO)-mediated signaling in CRF release. IL-2 stimulates CRF release in both regions, in a calcium- and dose-dependent manner. Nitroprusside, an NO generator, also induces CRF release. This IL-2-induced CRF release is antagonized by Ng-methyl-L-arginine and hemoglobin, known NO antagonists. Finally, norepinephrine and acetylcholine induce CRF release. The norepinephrine-induced CRF release is antagonized by phentolamine and propanolol and the acetylcholine-induced release by atropine and mecamylamine, which suggests the involvement of both alpha and beta adrenergic receptors and both muscarinic and nicotinic receptors. The acetylcholine-induced CRF release is antagonized by Ng-methyl-L-arginine, but the norepinephrine-induced response is not. These data support the suggestion that the amygdala may participate in communications between the neuroendocrine and immune systems.
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PMID:Interleukin-2 (IL-2) induces corticotropin-releasing factor (CRF) release from the amygdala and involves a nitric oxide-mediated signaling; comparison with the hypothalamic response. 785 99

In a previous study, we observed that a cell-free Salmonella typhimurium extract induced suppression of mitogen-induced T-cell proliferation and that this suppression involved nonresponsiveness of T-cells to interleukin-2 (IL-2) and augmentation of IL-2 receptor (IL-2R) expression. In this study, we found that inhibition of phytohemagglutinin (PHA)-stimulated murine spleen cell proliferation induced by a cell-free S. typhimurium extract was reversed by treatment with an anti-interferon-gamma monoclonal antibody (anti-IFN-gamma Ab), but not by interleukin-4 or NG-monomethyl-L-arginine, which is known to inhibit nitric oxide (NO)-secretion from spleen cells in culture. However, IL-2R expression was augmented by treatment with the extract, although this was independent of an NO-mediated mechanism. Only anti-IFN-gamma Ab treatment reduced the augmented IL-2R expression to a normal level. These results suggest that the suppression of T-cell proliferation induced by the Salmonella cell-free extract is associated with augmentation of IL-2R expression in an NO production-independent manner.
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PMID:Inhibition of T-cell proliferation induced by a cell-free Salmonella typhimurium extract does not involve a nitric oxide-mediated mechanism. 789 93

Many of the biological activities of cytokines are similar to clinical manifestations and abnormalities of laboratory parameters observed in chronic liver diseases (CLD). Evidence of impaired cytokine synthesis in CLD comes from studies of serum or plasma levels, supernatants of peripheral blood mononuclear cells stimulated with various agents and from studying cytokine expression locally in the liver. Circulating levels of several cytokine-regulated molecules such as neopterin, soluble IL-2 receptor, adhesion molecules, and metabolites of the nitric oxide pathway are elevated in patients with CLD. Thus inhibition of cytokine synthesis or modulation of their activity could provide not only important information about their pathophysiologic relevance but also have a profound impact on disease progression in CLD. These studies will also show whether prolonged anti-cytokine treatment with interleukin-1- or tumor necrosis factor-inhibitors interferes with host defense mechanism.
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PMID:The role of cytokines in the pathophysiology of chronic liver diseases. 812 73

The addition of nitric oxide (NO)-releasing agents, S-nitroso-N-acetyl-DL-penicillamine (SNAP), 1-hydroxy-2-oxo-2,3-bis(2-aminoethyl)-1-triazene (NOC18), 30{(+/-)-(E)-ethyl-2'-[(E)-hydroxyimino]-5-nitro-3-hexenecarbam oyl} -pyridine (NOR4) significantly inhibited NK cell activity against VZV-infected cells, while antibody-dependent cell-mediated cytotoxicity (ADCC) against VZV-infected cells was unaffected. Interferon-alpha (IFN-alpha) production by non-adherent peripheral blood mononuclear cells (NPBMC) cultured with VZV-infected cells was decreased by the addition of NO-releasing agents. Lymphocyte proliferation and the expression IL-2 receptor (CD25) in response to VZV antigen were also inhibited by the addition of NO-releasing agents. These results suggest that the production of NO by an inflammatory process may lead to inhibition of NK cell- and T cell-mediated immunity to VZV infection.
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PMID:Inhibition of natural killer (NK) cell activity against varicella-zoster virus (VZV)-infected fibroblasts and lymphocyte activation in response to VZV antigen by nitric oxide-releasing agents. 887 Jun 96

1. The biphasic nature of the potent modulatory action of interleukin-2 (IL-2) on hippocampal acetylcholine (ACh) release was investigated by use of brain slice superfusion. 2. Both the potentiating (10(-13) M) and inhibitory (10(-9) M) effects of IL-2 on hippocampal ACh release were stimulation-dependent and were blocked by a neutralizing IL-2 receptor antibody, suggesting the activation of typical IL-2 receptors in both cases. 3. Tetrodotoxin (TTX: 10 microM) failed to block the potentiation of ACh release induced by a very low concentration of IL-2 (10(-13) M) suggesting a direct effect on cholinergic nerve terminals. 4. In contrast, the inhibitory effect seen at a higher concentration (10(-9) M) was TTX-sensitive, and hence indicative of an indirect action. 5. To establish the nature of this intermediate mediator, blockers of nitric oxide synthesis, and of opioid and gamma-aminobutyric acid (GABA) receptors were used. Only GABAA and GABAB receptor antagonists altered the inhibitory action of IL-2, suggesting the participation of GABA as mediator. 6. Taken together, these results provide further evidence for the potent role of IL-2 in the modulation of cholinergic function in the rat hippocampus.
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PMID:Evidence for direct and indirect mechanisms in the potent modulatory action of interleukin-2 on the release of acetylcholine in rat hippocampal slices. 913 29

The cytokine, interleukin (IL)-15, and the T cell growth factor, IL-2, exhibit a similar spectrum of immune effects and share the IL-2 receptor (IL-2R) subunits IL-2Rbeta and IL-2Rgamma for signaling in hematopoietic cells. Numerous neuroregulatory activities of IL-2 have been suggested, but its expression in the normal central nervous system (CNS) is apparently very low and regionally restricted. We show by RNA and protein detection that IL-15, its specific receptor molecule, IL-15Ralpha, and the signal-transducing receptor subunits, IL-2Rbeta and IL-2Rgamma, are constitutively present in various regions of the developing and adult mouse brain. We further demonstrate, also at the single-cell level, that IL-15 and the components for IL-15Ralpha/IL-2Rbetagamma receptors are expressed by microglia. Tyrosine phosphorylation data are presented showing that IL-15 signaling in microglia involves Janus kinase 1 activity. At doses of 0.1-10 ng/ml, IL-15 affected functional properties of these cells, such as the production of nitric oxide, and supported their growth in culture, suggestive of a role as an autocrine growth factor. Microglial IL-15 could thus play a pivotal role in the CNS and may participate in certain CNS and neuroendocrine functions previously ascribed to IL-2.
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PMID:Mouse brain microglia express interleukin-15 and its multimeric receptor complex functionally coupled to Janus kinase activity. 936 Sep 52

In a previous study we demonstrated that Salmonella typhimurium-induced immunosuppression involved T-cell non-responsiveness to interleukin-2 (IL-2). In this study we observed that Salmonella-induced T-cell non-responsiveness to IL-2 was not reversed completely by treatment with N(G)-monomethyl-L-arginine, which is known to inhibit nitric oxide (NO) secretion by macrophages in culture. Furthermore, when purified splenic T-lymphocytes from Salmonella-infected mice were activated with an anti-CD3 antibody, the responsiveness of these T-cells to IL-2 was suppressed significantly. Results of flow cytometric analysis using an anti-IL-2 receptor gamma chain (IL-2Rgamma) antibody showed that IL-2Rgamma expression in mitogen-activated T-cells was down-regulated by Salmonella infection. These results suggest that Salmonella infection-induced T-cell non-responsiveness to IL-2 involves a defective function of T-cells themselves and appears to be regulated by inhibition of IL-2Rgamma expression in T-cells.
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PMID:Salmonella infection-induced non-responsiveness of murine splenic T-lymphocytes to interleukin-2 (IL-2) involves inhibition of IL-2 receptor gamma chain expression. 956 88

Mice spleen cells were incubated in vitro for 24 h with Pisum sativum agglutinin (PSA). The addition of these supernatants (SN) to macrophage cultures induced the production of nitric oxide (NO) by these cells in a dose-dependent manner. NO release was blocked in the presence of IFN gamma antibodies and partially inhibited by TNF alpha antibodies. The ability of PSA in inducing the production of IFN gamma and TNF alpha by spleen lymphocytes was confirmed assaying these cytokine levels in the SN. Spleen cells stimulated in vitro with PSA were highly activated showing an increased expression of the earlier activation marker, CD69, and a great proliferative response. On the other hand, spleen cells obtained from mice treated with PSA 24 h earlier, did not produce significant levels of IFN gamma or TNF alpha when incubated in vitro and showed a significantly lower proliferation rate when pulsed in vitro with PSA or Concanavalin A (ConA). The lower responsiveness to mitogens was also evident after 48 and 72 h after the treatment in vivo with the lectin. Nevertheless, the flow cytometric analysis of spleen lymphocytes obtained from PSA-treated animals showed a high degree of activation in cells CD3+. There was a decrease in the expression of L-selectin and VLA-4, when compared to controls, in parallel with a significant increase in the expression of CD69 and CD122 (IL-2R) in lymphocytes recovered from PSA-injected animals. The data point to evidence that PSA induces immunomodulatory effects, activating spleen lymphocytes in vivo, which become unresponsive to a second stimulation in vitro.
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PMID:Lymphocyte activation and cytokine production by Pisum sativum agglutinin (PSA) in vivo and in vitro. 1010 96

The effects of a recombinant factor IX product (BeneFix), and of five plasma-derived factor IX products, AlphaNine, Immunine, Konyne, Mononine and Replinine on in vitro peripheral blood mononuclear cell (PBMC) immune function were compared in a blinded study. We assessed the effects of these products on Con-A-induced lymphocyte proliferation and interleukin-2 and interleukin-10 secretion, expression of lymphocyte activation markers, and nitric oxide secretion by stimulated mouse peritoneal macrophages. At 1 mL-1 for 48 h, Konyne reduced Con-A-induced mitogenesis by 50% (P < 0.05); AlphaNine, Mononine and BeneFix had no effect. At 10 IU mL-1, Con-A-induced mi- togenesis was at control levels with Mononine and BeneFix, but was reduced to <15% (P < 0.05) with each of the other products. IL-2 and IL-10 secretion by Con-A-stimulated lymphocytes was also markedly depressed by all the products tested except Mononine and BeneFix. Dialysis of these products did not substantially affect these results. Flow cytometric analysis of lymphocyte activation markers following Con-A stimulation showed that Konyne also decreased IL-2 receptor alpha and beta chain (CD25 and CD122) induction on PBMC. Konyne also inhibited nitric oxide secretion to levels <18% of controls. These results indicate that certain factor IX products, including some of purported higher purity, substantially depress in vitro immune function. The importance of these findings to in vivo immune function in haemophilia B patients remains to be established.
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PMID:Immunosuppressive effects of factor IX products: an in vitro study. 1058 29


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