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)

In the immunosuppressed burn patient serum levels of both IL-2 and a soluble form of IL-2 receptor alpha (sIL-2R alpha) are significantly elevated. Strikingly, the production of these markers by the in vitro activated patients' cells is decreased. This study examines the role of IL-2 in the decreased production of the sIL-2R alpha in vitro in patients with major burns (n = 18, 30 to greater than 70% total body surface area). Peripheral blood mononuclear cell (PBMC) cultures from patients with highly elevated serum sIL-2R alpha, and from healthy controls (n = 12) were activated with concanavalin A (Con A) at initiation. In patients' cultures mitogen-induced increments of sIL-2R alpha levels were significantly lower. There was a significant negative correlation (r = 0.64, P less than 0.001) between a high serum sIL-2R alpha level and a decreased lectin-induced sIL-2R alpha release in vitro. Low levels of sIL-2R alpha in patients' samples were not normalized by increasing the number of T lymphocytes. Also exogenous rIL-1 was without effect, whereas rIL-3 increased sIL-2R alpha release in some cultures. However, sIL-2R alpha levels were significantly increased in patients' cultures by (i) addition of exogenous IL-2; (ii) removal of adherent cells; (iii) addition of cyclooxygenase inhibitor, indomethacin; (iv) bypassing cell surface activation by the combination of the calcium ionophore A23187 and the phorbol ester 12-o-tetradecanoyl acetate. The cyclic AMP-elevating drug, forskolin, abrogated the ability of exogenous IL-2 to increase sIL-2R alpha production. Thus, in the burn patient, the reduced in vitro sIL-2R alpha release appears to relate to abnormalities in IL-2 production and action mediated through its functional surface receptor. Elevated levels of sIL-2R alpha in vivo may, therefore, reflect systemic activation of T lymphocytes in response to biologically active IL-2.
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PMID:IL-2 regulation of soluble IL-2 receptor levels following thermal injury. 138 3

We analyzed cellular interactions between T lymphocytes and a recently established immortal glial line, L3 that retains several properties of immature oligodendrocytes (Aloisi et al., J Neurosci Res 27:16-24, 1990). L3 oligodendrocytes (L3-OL) cannot be induced to express class II antigens, nor do they specifically present antigen to syngeneic specific T lymphocyte. However, L3-OL strongly enhance the proliferation of freshly activated, interleukin-2(IL-2)-dependent T-line lymphocytes and concanavalin A (ConA)-activated lymphoblasts, irrespective of their antigen specificity or surface phenotype (CD4+ or CD8+). Resting and some activated T cells were susceptible to the mitogenic effect of L3-OL only in the presence of exogenous IL-2, not of other cytokines. The mitogenic effect of L3-OL did not depend on cell viability. It was observed in paraformaldehyde-fixed L3-OL cells and in membrane preparations, but not in culture supernatant. Neither intact L3-OL cells nor membrane preparations had direct IL-2 activity. The conclusion that the mitogenic effect of L3-OL cells is exerted by membrane structures acting as a costimulatory factor(s) of IL-2 is supported by the finding that it is largely blocked by a monoclonal anti-IL-2 receptor antibody. The effect is distinct from membrane-bound IL-1, membrane-bound tumor necrosis factor-alpha (TNF-alpha), IL-3, or IL-6 and cannot be reconstituted by these cytokines.
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PMID:Interaction between oligodendroglia and immune cells: mitogenic effect of an oligodendrocyte precursor cell line on syngeneic T lymphocytes. 138 59

The molecular mechanism of erythroid differentiation has been still ill-defined. In this study, we introduced a human interleukin-2 receptor (IL-2R) beta chain cDNA into ELM-I-1 cells which differentiated into hemoglobin-positive cells in the presence of erythropoietin (Epo), and established the transformant which expressed IL-2R beta chain. In this transformant, we revealed that IL-2 induced erythroid differentiation and the same pattern of tyrosine phosphorylation as Epo. These data suggest that tyrosine phosphorylation is involved in signal transduction pathway of erythroid differentiation. It is also implicated that the Epo and IL-2 receptor system share a common signal transduction pathway.
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PMID:Interleukin-2 (IL-2) induces erythroid differentiation and tyrosine phosphorylation in ELM-I-1 cells transfected with a human IL-2 receptor beta chain cDNA. 138 86

Cytolytic T lymphocytes (CTL) require soluble proteins termed lymphokines to develop lytic activity. In this report we have studied two of the lymphokines involved in the development of CTL during the allogeneic mixed leucocyte reaction (MLR). High doses of dendritic cells induced lytic activity from purified CD8+ cells in both the murine and human MLR. Under these conditions, IL-2 and IL-6 were endogenously produced and secreted. Antibodies to IL-2 or the IL-2 receptor blocked CTL formation; however, anti-IL-6 receptor antibodies only partially inhibited the response while anti-IL-6 antibodies were largely ineffective. When limiting numbers of antigen-presenting cells were used CTL failed to develop, and neither IL-2 nor IL-6 was secreted into the culture supernatant. Although the addition of IL-6 to such cultures was ineffective in generating CTL, the combination of IL-2 and IL-6 resulted in a 4-5-fold increase in lytic activity over that of IL-2 alone. We conclude that in the allogeneic MLR, IL-2 and IL-6 contribute to the generation of lytically active CD8+ cells, and the effect of IL-6 is evident when the dose of antigen-presenting cell is limited.
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PMID:IL-6 enhances the generation of cytolytic T lymphocytes in the allogeneic mixed leucocyte reaction. 138 65

This study tested the immunomodulatory effects of AS101, a synthetic organotellurium compound, on interleukin (IL-2) production and functional activity of normal human lymphocytes. Normal human lymphocytes were treated in vitro with 8-methoxypsoralen alone, ultraviolet A (UVA) and psoralen plus UVA (PUVA) as well as with a combination of AS101 + phytohaemagglutinin (PHA)+phorbol myristate acetate (PMA) and the above-mentioned treatments. Following treatment IL-2 production, free IL-2 receptor (IL-2R), the ability of lymphocytes to induce a local graft-versus-host reaction (GVHR) and the ability of separated CD4 cells to induce help were tested. 8-Methoxypsoralen alone did not significantly affect either cell proliferation or IL-2 production or functional activity. However, UVA and PUVA had a high inhibitory effect on cell proliferation, IL-2 production, IL-2R release and the functional activity of T- and T-helper lymphocytes. In the present study, the addition of AS101 and PMA serve to restore the impaired IL-2 production, T- and T-helper lymphocyte functional activity, but not the IL-2R release. AS101 alone without PMA was also effective in restoring GVHR and helper activity of CD4 lymphocytes, without affecting cell proliferation.
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PMID:Immunomodulatory effects of AS101 on interleukin-2 production and T-lymphocyte function of lymphocytes treated with psoralens and ultraviolet A. 139 Jan 19

Mouse interleukin-2 (mIL-2) proteins with substitutions at two residues (D34 and Q141) that interact specifically with different signalling subunits (respectively, beta and gamma) of the IL-2 receptor (IL-2R) were examined using several in vitro cellular assays. Proteins with specific substitutions at both residues were partial agonists and their maximal responses varied widely in different IL-2-responsive cell types. Two of these cell types had comparable numbers of IL-2R and similar affinities for wild-type mIL-2 and mutant mIL-2 proteins. However, the more responsive cell type had 'spare' IL-2R. Various mIL-2 proteins with substitutions at Q141 had modest defects in IL-2R-binding and were potent antagonists of native mIL-2 action. Proteins with bulky or basic substitutions at residue D34 were weak antagonists due to severely reduced IL-2 binding and their reduced binding paralleled their defects in IL-2R activation. Our results suggest that interaction of mIL-2 with IL-2R beta is more important for binding than activation and that the converse holds for mIL-2 interaction with IL-2R gamma. Also genetic manipulation of the interaction of IL-2 with IL-2R beta and IL-2R gamma has led to the discovery of potentially useful IL-2 antagonists and selective agonists.
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PMID:Receptor antagonist and selective agonist derivatives of mouse interleukin-2. 139 84

The cytochalasans, fungal metabolites that interact with actin, can affect lymphocyte proliferation; high concentrations inhibit lectin-induced proliferation and low concentrations augment it. The phorbol ester tumor promoter, PMA, alone is not mitogenic for primary lymphocytes but enhances the activity of mitogenic lectins. Because the cytochalasans have been reported to increase intracellular Ca2+ and because PMA activates protein kinase C, lymphocytes were treated with PMA and cytochalasin B (CyB) to determine if this combination would induce DNA synthesis. While this treatment by itself did not cause proliferation, lymphocytes cultured with PMA and CyB overnight, washed, and recultured with IL-2 proliferated to the same degree as lymphocytes stimulated with Con A. Three different cytochalasans, cytochalasin B, cytochalasin D, and chaetoglobosin C, all of which bind to cellular actin with different affinities and only one of which affects glucose transport, induced IL-2 receptors in combination with PMA. Flow cytometric analysis with an antibody to the IL-2 receptor alpha subunit confirmed the induction of receptors on CD8+ cells. However, no IL-2 was produced after the exposure of lymphocytes to the combination of cytochalasans and PMA. Therefore, there was sufficient signal to induce IL-2 receptor expression but not to induce IL-2.
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PMID:Cytochalasans and PMA induce IL-2 receptors on CD8+ lymphocytes. 139 84

We have studied the effects of uremic serum on the activation state and function of normal lymphocytes in vitro, by examining both accessory cell-dependent and accessory cell-independent responses. Uremic serum was obtained from patients on conservative treatment and from the same patients after they have undergone six months of maintenance hemodialysis. Uremic serum inhibited the proliferative responses to mitogens and to recombinant IL-2 (rIL-2) of both peripheral blood mononuclear cells (PBMC) and purified T cell populations. However, the responsiveness to IL-2 of pre-formed lymphoblasts, obtained from both PBMC and purified T cells, in the presence of uremic serum was similar to that obtained in the presence of normal serum, or was even enhanced. Uremic serum did not affect the cellular IL-2 receptor alpha (IL-2R) generation though it inhibited significantly the release of soluble IL-2 receptor (sIL-2R) and the production of IL-2 after mitogenic stimulation. Uremic serum from patients after six months of hemodialysis enhanced, but did not completely restore, proliferative responses and IL-2 production by control PBMC. Neither IL-1 nor IL-2R, which are present at elevated concentrations in uremic serum, appeared to be responsible for serum effects on in vitro responses of control lymphocytes. In conclusion, our results indicate that uremic serum affects both accessory cell-mediated and accessory cell-independent normal T cell responses. Uremic serum inhibition of T cell proliferation is associated with down-regulation of IL-2 synthesis by lymphocytes and the induction of an abnormal state of activation of lymphoblasts which is further enhanced following chronic hemodialysis.
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PMID:Uremic serum effects on peripheral blood mononuclear cell and purified T lymphocyte responses. 140 46

Theileria annulata-infected cells were cultured in the presence or absence of human recombinant interleukin 2 (hrIL-2). This growth factor proved to be capable of enhancing the growth of the infected cells: its effect was marked, particularly when the cells were seeded at low densities, and it varied from cell line to cell line. The infected cells produced a factor that possessed the biological activities of IL-2, since their supernatants could enhance the proliferation of concanvalin A-stimulated (Con A) blasts. The reactivity of the parasitized cells to hrIL-2 was abolished following their treatment with the antitheilerial drug buparvaquone. In addition, the drug inhibited the binding of 125I-IL-2 to T. annulata-infected cells but failed to suppress its binding to Con A blasts. Northern blot analysis revealed that the drug had no effect on the expression of the alpha chain of the IL-2 receptor (IL-2R). Therefore, it is possible that buparvaquone interferes with the expression of the beta chain of the IL-2R. The role of IL-2 and the IL2R in the permanent proliferation of T. annulata-infected cells is discussed.
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PMID:Effect of buparvaquone on the expression of interleukin 2 receptors in Theileria annulata-infected cells. 140 27

Fc receptor-positive lymphocytes (FcR+) contain lymphokine-activated killer cell (LAK) precursors that in response to IL-2 develop potent antitumor cytotoxicity. These FcR+ cells are also capable of antibody-dependent cytotoxicity (ADCC), which can be detected using fresh human peripheral blood lymphocytes (PBL) directed to murine targets, however, PBL-mediated ADCC to human tumors usually is very low, requiring a stimulation of the PBL, which also can be accomplished with IL-2. Using human melanoma tumor target cells, with and without the 14G2a monoclonal antibody, we examined in parallel the role of p75 IL-2 receptor for regulation of the induction of both LAK and ADCC forms of antitumor cytotoxicity. Enrichment of FcR+ cells from fresh peripheral blood by elutriation and flow cytometry, followed by varying periods of IL-2 culture, revealed a differential kinetics of activation. ADCC was detectable after PBL exposure to IL-2 for as short as the 4 h cytotoxicity assay, while LAK activation required more than 24 h of exposure. Elimination of the FcR+ cells by magnetic bead depletion from large granular lymphocyte populations (LGL) resulted in a loss of both LAK and ADCC. Addition of antibody known to block the binding of IL-2 to the p75 molecule of the IL-2 receptor complex (Mik-beta 1) to activation cultures at zero time resulted in abrogation of both cytotoxicities. These results suggest that differentiation and maturation of the ADCC effectors occurs in response to IL-2 via the p75 molecule, as also does LAK activation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Tumor recognition and lytic competence of IL-2-activated lymphocytes: regulation of both antibody-independent and -dependent cellular cytotoxicity via P75 IL-2 receptor. 142 May 99

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