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)

Although the effects of mitogens on the synthesis of interleukin-2 (IL-2) and IL-2 receptor (IL-2r) have been described, a detailed in situ analysis of the spatio-temporal changes of the expression of the IL-2 gene and the three IL-2r components in lymphoid tissues is still missing. Therefore, we analyzed the IL-2 and IL-2r expression after a staphylococcal enterotoxin A (SEA)-induced T cell activation on a cellular and anatomical basis in the Wistar rat. SEA caused a rapid induction of IL-2 mRNA in T cells of spleen, lymph node, and thymus, followed by the appearance of high systemic IL-2 serum levels (5 ng/ml), and a significant increase of CD25 on CD4+ and CD8+ lymphocytes. The histotopographic analysis of the IL-2r chains revealed a strong upregulation of IL-2r alpha (alpha) and IL-2r beta (beta) mRNAs in similar T cell specific compartments of spleen, lymph node, and thymus as seen for IL-2 mRNA. The abundant constitutive expression of IL-2r gamma (gamma) mRNA was unaffected by SEA. The parallel upregulation of IL-2, IL-2ralpha, and beta chains in conjunction with the continuous presence of the IL-2rgamma chain predominantly in T cell regions of immune organs suggests that the biological effects of IL-2 are essentially limited to T cells, at least after superantigen stimulation.
Cytokine 2003 Jun 21
PMID:Plasticity of IL-2 and IL-2 receptor chains in rat lymphoid tissues in situ after stimulation with staphylococcal enterotoxin A. 1289 Apr 48

We investigated the effects of pro-inflammatory cytokines of pericardial fluid on hemodynamic parameters in patients undergoing coronary artery surgery. Seventy-eight patients were included in the study and they were allocated to three groups: group 1, stable angina pectoris (SAP, n = 15); group 2, unstable angina pectoris (USAP, n = 34); group 3, post-myocardial infarction (PMI, n = 29). Pericardial fluid and arterial blood samples were obtained from all patients and interleukin (IL)-1beta, IL-2 receptor, IL-6, IL-8 and tumor necrosis factor-alpha (TNF-alpha) levels were measured. Pericardial IL-1beta concentration (pg/mL) was significantly higher in the USAP group (26.6 +/- 10.9) compared to the SAP (5.0 +/- 0.1) and PMI (5.8 +/- 1.0) groups. IL-2R, IL-6, IL-8 and TNF-alpha concentrations of pericardial fluid were significantly higher than serum in all groups; difference was more prominent in the PMI group compared to the SAP and the USAP groups. Serum IL-1beta concentrations (pg/mL) were significantly higher in the USAP group (21.8 +/- 3.4) compared to the SAP group (5.0 +/- 0.1) and the PMI group (5.4 +/- 1.6). Cardiac index (CI) before opening the pericardial sac was found to be lower in the USAP group (1.6 +/- 0.3 L/min/m2) compared to the SAP (2.2 +/- 0.5 L/min/m2) and the PMI (2.1 +/- 0.5 L/min/m2) groups (p = 0.028 and p = 0.011, respectively). In the USAP group, there was a relationship between reduction of CI and increase of IL-1beta levels in serum and pericardial fluid.
Cytokine 2003 Jul
PMID:Effect of pericardial fluid pro-inflammatory cytokines on hemodynamic parameters. 1290 54

Parameters of humoral and cellular immunity were investigated in pigs experimentally infected with a modified-live European porcine reproductive and respiratory syndrome virus (PRRSV, strain DV). PRRSV was detected by real-time RT-PCR and PRRSV-specific antibodies by a commercial ELISA test-kit, respectively. Interleukins IL-1alpha, IL-2, IL-4, IL-6, IL-8, IL-10, tumor necrosis factor (TNF-alpha) and interferon-gamma (IFN-gamma) as well as IL-2 receptor (IL-2R) were quantified at mRNA level using RT-PCR. Subpopulations of blood lymphocytes were assayed using flow cytometry. No significant changes neither in cytokine expression nor in shifts of CD4 and CD8 markers could be found, but similar curve diagrams concerning CD8 single positive T cells could be observed in all vaccinated animals with an initial decrease and an increase between post-infection days (PIDs) 7 and 14. In the vaccination group, TNF-alpha and IL-6 tended to be increased at PIDs 22 and 40, whereas no increase could be seen in IFN-gamma. When comparing the in vivo immune response to that being seen in in vitro experiments, similar shifts of CD4/CD8 lymphocyte subpopulations may be seen. Cytokine curve diagrams, however, do not reflect the in vitro findings to that extent.
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PMID:Parameters of humoral and cellular immunity following vaccination of pigs with a European modified-live strain of porcine reproductive and respiratory syndrome virus (PRRSV). 1458 48

Proliferation of activated T cells and CD56 bright natural killer (Cytokine Growth Factor Rev 13:169-183, 1995) cells caused by interleukin-2 (IL-2) has been exploited in IL-2-based therapies for the treatment of metastatic renal cell carcinoma and melanoma (J Clin Oncol 13:688-696, 1995; J Clin Oncol 17: 2105-2116, 1999). In this study, we demonstrate the potentially improved therapeutic value of IL-2 variants engineered to gain 15- to 30-fold increased affinity for the IL-2 receptor alpha-subunit (IL-2Ralpha). A novel pulsed bioassay was used to more closely approximate the rapid systemic clearance pharmacokinetics of cytokines such as IL-2, compared with conventional static bioassays. In this assay, mutants with increased affinity for IL-2Ralpha exhibit significantly increased activity for T-cell proliferation, whereas static bioassays not only fail to reveal the increased activity resulting from enhanced IL-2Ralpha affinity (false negatives), but also suggest improved activity for another mutant without enhanced activity in the pulsed assay (false positive). Our studies on the mechanism leading to increased activity of IL-2 mutants with increased IL-2Ralpha affinity suggest that cell-surface IL-2Ralpha acts as a ligand reservoir for the IL-2 mutants. This leads to increased cell-surface persistence of the IL-2 mutants with increased IL-2Ralpha affinity in cell-surface ligand reservoirs and consequently increased integrated growth signal. Furthermore, a mathematical model predicts increased persistence of cell surface-bound IL-2 in vivo for enhanced IL-2Ralpha-binding IL-2 mutants, suggesting potentially improved therapeutic value of allowing cellular capture of ligands in persistent cell-surface reservoirs. Finally, our findings emphasize the critical choice of appropriate bioassays to evaluate engineered proteins and other drugs.
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PMID:Interleukin 2 (IL-2) variants engineered for increased IL-2 receptor alpha-subunit affinity exhibit increased potency arising from a cell surface ligand reservoir effect. 1538 40

Interleukin-2 administration induces CD4 T cell expansion in HIV-infected patients, however, toxicity can limit dosing. BAY 50-4798 is a recombinant IL-2 analog with >1000-fold specificity for the high-affinity IL-2 receptor. The effects of this compound on unstimulated human PBMC were evaluated. PBMC from HIV(-) and HIV(+) donors were cultured in vitro with incremental doses of BAY 50-4798 or aldesleukin. CD25 expression and proliferation were evaluated with flow cytometry. Cytokine levels were measured by ELISA in culture supernatants. BAY 50-4798 induced dose-dependent increases in CD25 expression and proliferation of T cells, NK, and B cells and showed selectivity for CD4 T cells expressing CD25. Induction of pro-inflammatory cytokines was also dose-dependent and was observed at the concentrations of BAY 50-4798 with the highest biologic activity. These data suggest that BAY 50-4798 can induce proliferation of unstimulated T cells but loss of T cell selectivity and induction of pro-inflammatory cytokines occur at concentrations exerting the highest biologic activity.
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PMID:BAY 50-4798, a novel, high-affinity receptor-specific recombinant interleukin-2 analog, induces dose-dependent increases in CD25 expression and proliferation among unstimulated, human peripheral blood mononuclear cells in vitro. 1550 89

IL-2-induced vascular leak syndrome (VLS) is an important mechanism explaining the toxic effects of this cytokine and limiting its therapeutic use. We previously characterized a mouse model of IL-2-induced pulmonary VLS used to demonstrate that NK lymphocytes are involved in early/acute phase VLS (after one IL-2 injection). We also showed that NK cells and polymorphonuclear neutrophils (PMN) are involved in the late/chronic phase of the syndrome (after four daily IL-2 injections). In this study we use our mouse model to evaluate the role played by the IL-2 receptor (IL-2R) in VLS induction. Mouse and human IL-2R are different since the mouse IL-2Rbeta chain does not recognize IL-2. Here, we compare the acute and late VLS responses in human IL-2Rbeta transgenic and C57BL/6 wild type mice. Parameters linked to early phase VLS (bronchoconstriction and PMN mobilization) are enhanced in human IL-2Rbeta transgenic mice. By contrast, parameters used to measure late events (protein leakage and edema) are similar in human IL-2Rbeta transgenic mice and C57BL/6 wild type animals. However, after four IL-2 injections, the cellular content of the bronchoalveolar lavage fluids was different between the two types of animals. This study also characterizes a humanized animal model that could be further used to study human IL-2 activity and side effects in vivo.
Cytokine 2005 Dec 21
PMID:Constitutive expression of IL-2Rbeta chain and its effects on IL-2-induced vascular leak syndrome. 1637 32

Recombinant interleukin-2 (IL-2) (aldesleukin, Proleukin, Chiron, Emeryville, CA) is approved for treatment of cancer patients and under investigation in HIV-infected individuals. However, treatment with aldesleukin is associated with toxicity, which may be due to its elicitation of inflammatory mediators from cells that express the intermediate-affinity IL-2 receptor. BAY 50-4798, a novel IL-2 analog, is a selective agonist for the high-affinity receptor. It induces the proliferation of activated T cells with a potency similar to that of aldesleukin but has reduced activity on cells expressing the intermediate-affinity receptor. In the current study, we compared cytokine responses elicited in peripheral blood mononuclear cell (PBMC) cultures stimulated with BAY 50-4798 or aldesleukin. BAY 50-4798 induced approximately 5-fold lower mean levels of endogenous IL-2 than aldesleukin, and at least 50% lower levels of proinflammatory cytokines, such as tumor necrosis fctor-alpha (TNF-alpha), IL-1beta, IL-6, and interferon-gamma (IFN-gamma). Furthermore, statistically significant reductions in the levels of IL-5, IL-8, IL-10, IL-13, and granulocyte-macrophage colony-stimulating factor (GM-CSF) were observed in response to BAY 50-4798. These findings increase our understanding of the biologic action of BAY 50-4798 and suggest a mechanism by which it may exhibit better safety than aldesleukin in humans.
J Interferon Cytokine Res 2006 Mar
PMID:Reduced secondary cytokine induction by BAY 50-4798, a high-affinity receptor-specific interleukin-2 analog. 1654 39

Treatment of Nylon wool-passed cells (NWC) prepared from the spleen of C57BL/6 mice with IL-18 and IL-12, but not with IL-18 alone, resulted in induction of IFN-gamma, a Th1 cytokine, and GM-CSF at 24 h, and IL-13, a Th2 cytokine at 72 h. The induction of IL-13 was suppressed by anti-GM-CSF antibody, indicating involvement of GM-CSF in IL-13 production. When NWC incubated with IL-18 and IL-12 for 72 h ("primary treatment") were treated again with the same cytokines ("secondary treatment"), IL-13 was induced much more quickly than observed in the primary treatment. Flow cytometric analysis of NWC after the primary treatment showed marked increases in the CD4(-)CD8(-) non-T cell population bearing CD25(+), CD45RB(super high) and CD122(+). These cells were positive for CD49b but negative for NK1.1, indicating that they were not typical but NK-like cells. The NK-like cells produced IL-13 in response to the treatment with IL-18 alone, indicating that the generation of these cells in the primary treatment likely accounts for the quick production of IL-13 in the secondary treatment. These results show that IL-18 and IL-12 generates the NK-like cells in NWC by a process mediated by GM-CSF that are ready for producing IL-13.
Cytokine 2006 Feb 21
PMID:Production of IL-13 in spleen cells by IL-18 and IL-12 through generation of NK-like cells. 1654 65

Apoptosis of active T lymphocytes constitutes a major control mechanism of immune homeostasis and tolerance. In Crohn's disease, abnormal activation of mucosal T lymphocytes against enteric bacteria is the key event triggering intestinal inflammation. Resistance of lymphocytes to apoptosis has been proposed as the pathogenetic defect. We examined the influence of bacteria-mucosa interactions on apoptosis of mucosal T lymphocytes. Ileal specimens were obtained at surgery from 12 patients with Crohn's disease. Mucosal explants from each specimen were cultured with nonpathogenic Escherichia coli ATCC 35345, Lactobacillus casei DN-114 001, or no bacteria. Cytokine release was measured in supernatant, and mononuclear cells were isolated for phenotypic characterization and Bcl-2 family protein expression. Coculture of inflamed tissue with L. casei significantly reduced the release of interleukin (IL)-6 and tumor necrosis factor alpha (P < 0.05). In addition, coculture with L. casei significantly reduced the number of T cells displaying the IL-2 receptor in the lamina propria. Expression of the antiapoptotic protein Bcl-2 in lamina propria lymphocytes was also reduced after coculture with L. casei, and the percentage of deoxyuridine triphosphate nick-end labeling positive lymphocytes increased. The nonpathogenic E. coli strain had no significant effect. In conclusion, L. casei reduces the number of activated T lymphocytes in the lamina propria of Crohn's disease mucosa. A balanced, local microecology may restore immune homeostasis.
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PMID:Modulation of apoptosis in intestinal lymphocytes by a probiotic bacteria in Crohn's disease. 1664 Nov 37

The NK1.1 molecule participates in NK, NKT, and T-cell activation, contributing to IFN-gamma production and cytotoxicity. To characterize the early immune response to Plasmodium chabaudi AS, spleen NK1.1(+) and NK1.1(-) T cells were compared in acutely infected C57BL/6 mice. The first parasitemia peak in C57BL/6 mice correlated with increase in CD4(+)NK1.1(+)TCR-alphabeta(+), CD8(+)NK1.1(+)TCR-alphabeta(+), and CD4(+)NK1.1(-)TCR-alphabeta(+) cell numbers per spleen, where a higher increment was observed for NK1.1(+) T cells compared to NK1.1(-) T cells. According to the ability to recognize the CD1d-alpha-GalCer tetramer, CD4(+)NK1.1(+) cells in 7-day infected mice were not predominantly invariant NKT cells. At that time, nearly all NK1.1(+) T cells and around 30% of NK1.1(-) T cells showed an experienced/activated (CD44(HI)CD69(HI)CD122(HI)) cell phenotype, with high expression of Fas and PD-L1 correlating with their low proliferative capacity. Moreover, whereas IFN-gamma production by CD4(+)NK1.1(+) cells peaked at day 4 p.i., the IFN-gamma response of CD4(+)NK1.1(-) cells continued to increase at day 5 of infection. We also observed, at day 7 p.i., 2-fold higher percentages of perforin(+) cells in CD8(+)NK1.1(+) cells compared to CD8(+)NK1.1(-) cells. These results indicate that spleen NK1.1(+) and NK1.1(-) T cells respond to acute P. chabaudi malaria with different kinetics in terms of activation, proliferation, and IFN-gamma production.
J Interferon Cytokine Res 2010 Jun
PMID:Comparative analysis of activation phenotype, proliferation, and IFN-gamma production by spleen NK1.1(+) and NK1.1(-) T cells during Plasmodium chabaudi AS malaria. 2018 75


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