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)

A monocytic cell line, THP-1, was acutely infected with HIV, and the effects of various factors including INF-gamma, LPS, IL-2, and IL-6 were analyzed. While IFN-gamma suppressed HIV production, IL-2 and IL-6 augmented it. The suppressive effect of IFN-gamma was not overcome by IL-2 or by LPS. We studied whether the induction of IL-2 receptor alpha (IL-2R alpha) expression by those factors was related to HIV infection or not. By immunofluorescence analysis using monoclonal anti-IL-2R alpha antibody, we observed that HIV infection itself induced IL-2R alpha expression moderately in U937 and THP-1, and IL-6 as well as IFN-gamma highly induced IL-2R alpha expression both in uninfected and infected THP-1. Although induction of HIV production and IL-2R alpha expression by cytokines seem not to be directly correlated, these results suggest that soluble IL-2R alpha increased in AIDS patients might be at least partly derived from infected monocyte/macrophages activated by various cytokines, especially IL-6, which is mainly produced by themselves.
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PMID:Effect of cytokines on HIV release and IL-2 receptor alpha expression in monocytic cell lines. 169 Dec 89

Because mice are more resistant than humans to the pathogenic effects of bacterial toxins, we used D-Galactosamine- (D-Gal) sensitized mice as a model system to evaluate potential toxic shock symptoms triggered by the superantigen staphylococcal enterotoxin B (SEB). We show that similar to endotoxin (lipopolysaccharide) [LPS], the exotoxin SEB causes lethal shock within 8 h in D-Gal-sensitized mice, inducing 100% and about 50% lethality with 20 and 2 micrograms SEB, respectively. The lethal shock triggered by the superantigen SEB is mediated by T cells, a conclusion based on the observation that T cell repopulation of SCID mice conferred sensitivity to SEB. Since CSA also conferred protection, the role of T cell-derived lymphokines in mediating lethal shock was evaluated. Within 30-60 min after SEB injection, serum tumor necrosis factor (TNF) levels peaked, followed immediately by interleukin-2 (IL-2). Serum-borne lymphokines were detected well in advance of signs of T cell activation, as assessed by IL-2 receptor expression of SEB-reactive V beta 8+ T cells. Passive immunization with anti-TNF-alpha/beta-neutralizing monoclonal antibody also conferred protection, indicating that it is TNF which is critical for initiating toxic shock symptoms. Taken together, this study defines basic differences between endotoxin (LPS)- and exotoxin (SEB)-mediated lethal shock, in that the former is mediated by macrophages and the latter by T cells. Yet the pathogenesis distal to the lymphokine/cytokine-producing cells appears surprisingly similar in that TNF represents a key mediator in inducing shock.
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PMID:T cell-mediated lethal shock triggered in mice by the superantigen staphylococcal enterotoxin B: critical role of tumor necrosis factor. 173 Sep 29

Mycophenolic acid (MPA), an inhibitor of inosine monophosphate dehydrogenase, in nanomolar concentrations blocks proliferative responses of cultured human, mouse and rat T lymphocytes and B lymphocytes to mitogens or in mixed lymphocyte reactions. The inhibitory effect of MPA on lymphocyte proliferation is reversed by addition to culture media of deoxyguanosine or guanosine but not by addition of deoxyadenosine or adenosine. The findings suggest that the principal mechanism of action of low concentrations of MPA is depletion of deoxyguanosine triphosphate which is required for DNA synthesis. In immunosuppressive doses, MPA does not affect the formation of IL-1 by LPS-activated human peripheral blood monocytes. Unlike cyclosporin A and FK-506, MPA does not inhibit the formation of IL-2 and the expression of the IL-2 receptor in mitogen-activated human T lymphocytes. MPA suppresses mixed lymphocyte reactions when added 3 days after their initiation. These findings suggest that MPA does not inhibit early responses of T and B lymphocytes to mitogenic or antigenic stimulation but blocks the cells at the time of DNA synthesis. The cytostatic effect of MPA is more potent on lymphocytes than on other cell types, such as fibroblasts and endothelial cells. MPA also inhibits antibody formation by polyclonally activated human B lymphocytes. MPA is an immunosuppressive agent reversibly inhibiting proliferation of T and B lymphocytes and antibody formation, with a profile of activity different from that of other immunosuppressive drugs. Human T and B lymphocytic and promonocytic cell lines are highly sensitive to the antiproliferative effects of MPA, whereas the erythroid precursor cell line K562 is less susceptible. The effect of MPA on cells of the monocyte-macrophage lineage could exert long-acting anti-inflammatory activity. MPA or analogues may have therapeutic utility in diseases such as rheumatoid arthritis, for prevention of allograft rejection and in lymphocytic or monocytic leukaemias and lymphomas.
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PMID:Lymphocyte-selective cytostatic and immunosuppressive effects of mycophenolic acid in vitro: role of deoxyguanosine nucleotide depletion. 182 93

The radioresistance of lymphocytes increases after mitogenic stimulation, suggesting that a radiosensitive activation event contributes to the overall radiosensitivity of lymphocytes. We have sought to identify this activation event by determining the extent of activation of mitogen-stimulated lymphocytes previously exposed to growth-inhibiting doses of radiation. Mouse splenic lymphocytes were exposed to 0-15 Gy 137Cs radiation, and structural and functional damage were assayed. Although damage to cellular thiols and nonprotein thiols was modest, there was a significant loss of viability by 6 h as determined by uptake of propidium iodide (PI). Since cells did not die immediately after irradiation, the activation events which remained were evaluated. Growth-inhibiting doses of radiation left cells partially responsive to mitogen, in that cells were able to exit G0 phase, but they could progress no further into the cell cycle than G1a phase. It is important to note that assessment of viability by uptake of PI indicated substantial cell death after 15 Gy (45%, 6 h; 90%, 24 h); however, cell cycle analysis at 24 h indicated no significant decrease in progression from G0 to G1a phase. The LPS-stimulated response of B cells was more radiosensitive than the Con A-stimulated response of T cells. Further analysis of the Con A response indicated that production of interleukin-2 (IL-2) was unaffected, but expression of the IL-2 receptor was inhibited. Inhibition of poly-ADP-ribosylation and damage to lipids did not prevent the lack of mitogen responsiveness, since neither the ADP-ribose transferase inhibitor 3-aminobenzamide nor lipid radical scavengers had restorative effects on the mitogenic response. Nor was Con A-stimulated incorporation of [3H]thymidine restored with inhibitors of prostaglandin or leukotriene synthesis, suggesting that inhibition was due to direct effects on the Con A responders, and not indirect effects mediated by arachidonate metabolites. These results indicate that growth-inhibiting doses of radiation trigger the process in lymphocytes that culminates in apoptosis, yet leave the cells partially responsive to mitogenic stimuli.
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PMID:Residual activation events functional after irradiation of mouse splenic lymphocytes. 198 2

In this study we investigated the ability of GM-1/P, a calcium mediated processed form of monosialoganglioside GM-1, of in vivo augmenting mouse T and B-lymphocyte blastogenesis induced by mitogens. We have also determined its effect on IL-2 responsiveness by analyzing the induction of the expression of IL-2 receptor (IL-2r) on mouse spleen cells. Lymphocyte blastogenesis was evaluated by 3H-TdR incorporation of spleen cells from untreated or GM-1/P (1mg/Kg, i.v., day-1) treated mice cultured in the presence of T (PHA, ConA) B (LPS) cell specific mitogens. The stimulatory effects appeared to be due to a direct action on T and B lymphocytes, since proliferative response was not abolished by removal of macrophages. Splenocytes from GM-1/P treated mice showed increased proliferation in response to various concentrations of HrIL-2; moreover under these conditions an increased generation of LAK activity was found. A direct evidence for enhanced expression of IL-2r was obtained by immunofluorescence and FACS analysis using a monoclonal antibody (PC.61) directed against the p55 subunit of murine IL-2r. 29% PC.61+ cells were found in IL-2 cultures from treated spleen cells.
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PMID:Enhancement of lymphocyte proliferation and IL-2 receptor expression by a processed form (GM-1/P) of monosialoganglioside GM-1. 209 40

It has been shown that the antithyroid drug methimazole (MMI) may affect B cells and possibly accessory cell function. In the present study we investigated in detail the effects of MMI on T cell in vitro proliferation. The following variables were evaluated: T cell proliferation following stimulation with phytohemagglutinin (PHA), and anti-CD3 or anti-CD2 monoclonal antibodies; interleukin-2 (IL-2) and gamma-interferon (gamma-IFN) production by PHA-stimulated T cells in bulk culture and by T cell clones; PHA-induced IL-2 receptor expression; LPS-induced interleukin-1 production by accessory cells. The results obtained failed to demonstrate any effect of MMI on T cells in vitro proliferation, whatever the activation pathway considered. In addition, IL-2 and gamma-IFN productions were substantially unaffected by the drug, as well as IL-1 production by accessory cells. However, a slight reduction of PHA-induced IL-2 receptor expression was observed. Although the hypothesis of an effect of MMI on some specialized T cell functions cannot be ruled out, it is likely that the supposed "immunosuppressive" effect of the drug does not concern primarily the T lymphocyte.
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PMID:The effect of methimazole on the immune system is unlikely to operate directly on T lymphocytes. 212 30

Small, resting B lymphocytes express few, if any, interleukin 2 (IL-2) receptors, but activated B cells may express such receptors. This paper examines the requirements for receptor expression. Normal murine splenocyte populations were enriched for B cells and cultured at relatively low density. IL-2 receptor expression was studied by measuring the binding of the anti-IL-2 receptor monoclonal antibody PC61. Lymphoblasts arising through stimulation by Escherichia coli lipopolysaccharide failed to express IL-2 receptors. B cells cultured with conditioned medium from concanavalin A-stimulated EL4 thymoma cells, with or without LPS, displayed IL-2 receptors. This bioactivity of EL4 conditioned medium could not be replaced by any concentration of B-cell-stimulatory factor 1 (IL-4), IL-1, IL-2, or IL-3 tested. However, the recently cloned lymphokine T-cell-replacing factor (IL-5) was a potent inducer of IL-2 receptor expression, as was the probably identical material known as eosinophil differentiation factor. The receptors so induced appeared to be functional, as receptor-expressing (but not control) lymphoblasts, responded to IL-2 by proliferation, indicative of high-affinity-receptor expression.
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PMID:T-cell-replacing factor (interleukin 5) induces expression of interleukin 2 receptors on murine splenic B cells. 311 Jul 87

The production of interleukin-1 (IL-1) and interleukin-2 (IL-2) by peripheral blood mononuclear cells (PBM) was assessed in multiple sclerosis (MS) patients in relapse, chronic progressive MS patients, patients with other neurological diseases (OND) and healthy subjects. Production was defined as the level of IL-1 and IL-2 in PBM supernatants. Neither spontaneous nor LPS-induced IL-1 production differed significantly in MS, OND patients or healthy individuals. On the other hand PHA-induced PBM IL-2 production was significantly less in MS patients in relapse (130 +/- 10.0 U/ml) than in chronic progressive MS patients (172 +/- 9.8 U/ml), OND patients (192 +/- 11.5 U/ml) and healthy subjects (215 +/- 13.8 U/ml) (P less than 0.02). Spontaneous IL-2 production was also diminished in MS patients in relapse (31 +/- 7.2 U/ml) as compared to chronic progressive MS patients (46 +/- 8.8 U/ml) and healthy subjects (49 +/- 11.1 U/ml) (P less than 0.01). Anti-Tac monoclonal antibody was used to study IL-2 receptor expression on the same sample of PBM that was used for IL-2 study. MS patients in relapse had significantly higher levels of IL-2 receptor-positive unstimulated PBM (6.0 +/- 2.2%) as compared to chronic progressive MS (2.0 +/- 0.9%), OND (2.5 +/- 1.1%) and healthy subjects (1.5 +/- 0.7%) (P less than 0.002). We postulate that reduced apparent IL-2 production by PBM of MS patients in relapse may result from immediate IL-2 binding to receptor expressed on activated T lymphocytes and internalization of IL-2-receptor complex.
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PMID:Interleukin-1 and interleukin-2 production by peripheral blood mononuclear cells in multiple sclerosis patients. 326 Feb 70

The B-cell differentiation-inducing activity of interleukin-1 (IL-1) was compared with that of T-cell replacing factor (TRF)/interleukin-5 (IL-5), which was originally described as a late-acting B-cell differentiation-inducing factor. Human recombinant IL-1 and murine recombinant TRF/IL-5 were used in this study. Purified B cells from non-primed or antigen-primed mice, LPS-stimulated B-cell blasts, and chronic B-cell leukaemia (BCL1) cells were used as the responding B-cell population. Addition of IL-1 to the culture of normal B-cells and sheep red blood cells (SRBC) induced a dose-dependent anti-SRBC IgM response, with maximal response at 100 U/ml, whereas the response induced by TRF/IL-5 was less than that induced by IL-1 and did not reach the maximum even at 100 U/ml. Addition of anti-IL-1 antibody, but not anti-TRF/IL-5 antibody or anti-IL-2 receptor antibody, inhibited IL-1-induced anti-SRBC responses. Depletion of cells adherent to Sephadex beads from splenic B cells showed no significant effect on the magnitude of the total responses. IL-1 could induce little, if any, differentiation in antigen-primed B cells, LPS-stimulated B-cell blasts, or BCL1 cells into antibody-secreting cells, whereas differentiation could be induced by low doses of TRF/IL-5 (1-2 U/ml). Of great interest is that suboptimal doses of IL-1 (10 U/ml) could synergize with TRF in the primary anti-SRBC PFC responses. Kinetic studies revealed that IL-1 acts on B cells for the first 2 days and TRF/IL-5 for the last 3 days in 5-day cultures of B cells. These results suggest that IL-1 acts primarily on resting B cells as a differentiation-inducing factor in the presence of antigen, and also acts as a 'priming' factor for TRF/IL-5.
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PMID:Role of recombinant interleukin-1 compared to recombinant T-cell replacing factor/interleukin-5 in B-cell differentiation. 328 Apr 72

The purpose of this study was to elucidate the mechanism of action of triptolide on the T-lymphocyte-mediated immune response. Lymphocytes were incubated with a suboptimal dose of Con A or PHA in the presence or absence of varying doses of triptolide to assess the effect of triptolide on lymphocyte proliferation, interleukin-2 (IL-2) production and IL-2 receptor expression. Then, Con A or PHA induced T-blast cells were cultured with a sufficient dose of recombinant human IL-2 in the presence or absence of triptolide to evaluate the effect of triptolide on the interaction of IL-2 and IL-2 receptors. The effect of triptolide on the immune response in vivo was also investigated. The results of these studies clearly demonstrated that triptolide selectively inhibited the T-lymphocyte proliferative response to Con A and PHA, but had less effect on LPS-induced B-lymphocyte proliferation. Triptolide also suppressed the expression of IL-2 receptors on PHA induced T-blast cells, but did not alter the production of IL-2 by mouse splenic cells and human tonsil lymphocytes. Furthermore, the results also showed that triptolide at higher concentration had a slight inhibitory effect on the interaction of IL-2 and IL-2 receptors, and addition of exogenous IL-2 did not reverse the inhibiting action of triptolide on T-cell proliferation. Taken together, these results suggest that triptolide inhibits T-lymphocyte proliferation mainly by affecting IL-2 receptor expression rather than IL-2 production.
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PMID:Triptolide suppresses T-lymphocyte proliferation by inhibiting interleukin-2 receptor expression, but spares interleukin-2 production and mRNA expression. 786 94


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