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Query: UNIPROT:P14784 (IL-2 receptor)
 3,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human tumors express high levels of growth factors and their receptors, and many types of malignant cells appear to exhibit autocrine- or paracrine-stimulated growth. Therefore, antireceptor directed therapies have the potential of being useful anti-cancer agents. A series of murine monoclonal antibodies (MAbs) directed against human growth factor receptors and their corresponding growth factors have been produced. MAbs against the receptors for epidermal growth factor, Her2/Neu, transferrin, insulin-like growth factor, interleukin, (IL)-2 and IL-1 are currently being evaluated. MAbs directed against epidermal growth factor, transforming growth factor-alpha, bombesin, IL-2, and IL-6 also are under study. These MAbs have shown promising preclinical activity, and some of them are being tested in clinical trials. So far, anti-tumor responses have been observed with anti-IL-2 receptor, anti-bombesin and anti-IL-6 MAbs. Further research is focusing in the production of "chimeric" and "humanized" MAbs, in order to obviate the problem of host immune reactions.
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PMID:Receptor blockade with monoclonal antibodies as anti-cancer therapy. 784 12

The biological significance of the signals triggered by the interaction of cell surface expressed LFA-1 and ICAM-1 has been investigated in Con A and immobilized anti-CD3 mAb stimulated cultures. When added at the beginning of activation in the presence of Con A, soluble anti-LFA-1 and anti-ICAM-1 mAbs could strongly inhibit cell proliferation. Such inhibitory effect was also exhibited in the proliferative response of thymocytes to immobilized anti-CD 3 mAb activation. However, the soluble anti-LFA-1 mAb was unable to inhibit the proliferation of primed thymocytes preactivated with Con A for 24 h or of IL-1 + IL-2 activated fresh thymocytes. Anti-LFA-1 mAb could profoundly inhibit Con A-induced thymocytes to produce IL-2 and IL-6 and to reduce IL-2 receptor expression. By contrast, anti-LFA-immobilized on plastic plates together with immobilized anti-CD 3 mAbs or CD 3 cross-linking with LFA-1 by secondary antibodies resulted in an enhanced activation signals for thymocytes to proliferate compared with that activated by anti-CD 3 alone. Thus, mAb to LFA-1 is a functional molecule for thymocyte activation, mediating signals contributed to very early phases of signal transduction through TCR/CD 3 pathway, and that LFA-1 might provide a costimulatory signal for expression of IL-2 R and IL-2 production.
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PMID:[Functional roles of LFA-1 involved in signal transduction for thymocyte activation]. 787 72

Major surgery suppresses host immune reactivity through alterations in monocyte and T cell-derived cytokine, eicosanoid and acute-phase protein release. Recombinant interleukin (IL) 2 augments T lymphocyte and monocyte activity in vitro. Eighteen patients, with localized colorectal cancer, were randomized to receive either recombinant IL-2 or placebo for 3 days by subcutaneous injection before surgery. Serum levels of IL-1 beta, IL-6, tumour necrosis factor alpha, soluble IL-2 receptor, C-reactive protein (CRP) and albumin were measured, and T lymphocyte surface expression of HLA-DR and CD25 and neutrophil phagocytosis were determined, before and for 21 days after surgery. Significant augmentation of IL-6, CRP and soluble IL-2 receptor production, enhanced expression of activation markers and increased neutrophil activity were found. Recombinant IL-2 may have a role in ameliorating the immunosuppression found after major surgery.
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PMID:Modulation of the cytokine and acute-phase response to major surgery by recombinant interleukin-2. 788 67

Several groups have now investigated the cytokine response to strenuous exercise. In this article we try to summarize known data on this topic. Significant, albeit mild increases in plasma levels of the monokines IL-1, TNF-alpha, IL-6, and of soluble IL-2 receptor have been reported following strenuous exercise. Increased excretion of cytokines after exercise can also be shown in the urine of athletes. Modulation of cytokine release by strenuous exercise can also be demonstrated using in vitro cell cultures. Several authors have shown an increase in endotoxin-stimulated monokine release following exercise. In contrast, using whole blood cultures we found strongly depressed production of interferon gamma (in response to mitogen or endotoxin) following strenuous exercise. The potential significance of cytokine modulation for exercise-related immunological problems is discussed.
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PMID:The cytokine response to strenuous exercise. 788 99

The immunomodulator ammonium trichloro(dioxyethylene-0-0')tellurate (AS101) has previously been found by us to have radioprotective properties when injected into mice before sublethal and lethal doses of irradiation. AS101 also was found to protect mice from hematopoietic damage caused by various chemotherapeutic drugs. Based on these findings, phase II clinical trials with cancer patients treated with AS101, in combination with chemotherapy, are currently underway. In the present study, we wanted to assess the role of several cytokines in the radioprotection conferred by AS101. We show that the administration of neutralizing antibodies against interleukin-1 (IL-1) receptor, IL-6 receptor, IL-6, tumor necrosis factor (TNF), or stem cell factor (SCF) completely abrogates the ability of AS101 to increase the survival of lethally irradiated mice. Moreover, the injection of each of these antibodies reduces the ability of AS101 to increase the number of BM, spleen cells, and the number of circulating neutrophils, lymphocytes, and platelets in irradiated mice. In addition, these antibodies abrogate the enhancing effect of AS101 on the secretion of IL-3, IL-6, and granulocyte-macrophage colony-stimulating factor, all of which decrease significantly in sublethally irradiated mice. By contrast, the injection of anti-IL-2 receptor antibody or control Igs to AS101-treated mice does not interfere with the radioprotective effects of the compound. These results suggest a role for IL-1, IL-6, TNF alpha, and SCF in the radioprotective effect of AS101. Because cytokine toxicity remains a significant concern, the clinical application of AS101, which has no toxicity, is particularly valuable.
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PMID:Role of endogenous cytokines secretion in radioprotection conferred by the immunomodulator ammonium trichloro(dioxyethylene-0-0')tellurate. 788 74

Patients with Hodgkin's disease (HD) frequently show elevated serum titers against human herpersvirus-6 (HHV-6) and their tissues contain significantly increased numbers of cells with HHV-6 DNA. This may coincide with similar data of Epstein-Barr virus (EBV) infections. According to in vitro studies, Hodgkin- and Reed-Sternberg (RS) cells can be infected by HHV-6 and may be coinfected by HHV-6 and EBV. Both viruses are potentially oncogenic and also may interfere with the production of various cytokines. We now demonstrate by using immunohistological methods that HHV-6 antigens are present in 77.3% of the HD lymphomas, 37% of which contain the replication-associated p41 "early-late" antigen and 63% the late membrane antigen complex gp116/64/54. Monocytic cell populations including HD and RS cells are most frequently antigen-positive, while lymphoid cells are less frequently. These cells also express IL-6 and IL-6 receptors as well as the IL-2 receptor a chain (CD25), while only occasionally the IL-2 receptor beta chain (p70). IL-6 receptors are significantly more frequently expressed than IL-6 itself. HD and RS cells constitute a significant pool of proliferating cells as reflected by their 95% positivity for PCNA, yet tumor suppressor genes are found in only 21% and the proto-oncogenes fes and met are expressed in various types of cells. The data may indicate that both viruses possibly contribute to the course of the disease through polyclonal stimulations of cell proliferation and coincident dysregulation of the cytokine network control of cell function and proliferation. A direct oncogenic effect of EBV and HHV-6 in HD appears less probable.
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PMID:Human herpesvirus-6 (HHV-6) in Hodgkin's disease: cellular expression of viral antigens as compared to oncogenes met and fes, tumor suppressor gene product p53, and interleukins 2 and 6. 789 77

Co-stimulation of highly purified peripheral T lymphocytes from healthy blood donors with the adhesion molecules CD2 and CD28 in association with recombinant interleukin-7 (rIL-7) induced T-cell proliferation, multiple cytokine secretion and IL-2 receptivity. We demonstrated that rIL-7 is as potent as rIL-2 in inducing the proliferation of unseparated, CD4+ and CD8+ T cells. In contrast to low or undetectable levels of IL-1 alpha, IL-6 and IL-2, high levels of tumour necrosis factor-alpha (TNF-alpha), IL-4 and granulocyte-macrophage colony-stimulating factor (GM-CSF) were secreted. Experiments using blocking antibodies suggested a direct mechanism for rIL-7 co-stimulatory effect, although induction of the CD25/IL-2 receptor alpha-chain (CD25/IL-2R alpha) was observed. Monoclonal antibodies (mAb) against the adhesion molecules CD2 and CD28 are likely to mimic the interaction with their respective physiological ligands [lymphocyte function-associated antigen-3 (LFA-3)/CD58, CD59 and CD48 for CD2, B7/BB1 for CD28]. Taken together, these in vitro data suggest that IL-7 could participate in paracrine interactions between T lymphocytes and thymic stromal cells or dendritic cells, via its potent co-stimulatory activity with CD2 and CD28 adhesion molecules.
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PMID:Interleukin-7 is a potent co-stimulus of the adhesion pathway involving CD2 and CD28 molecules. 790 90

Cytokine gene expression was determined in vivo in the lungs and spleens of Mycoplasma pneumoniae-infected BALB/c mice by means of qualitative and semiquantitative PCR-mediated mRNA amplification. During the acute phase of both primary and secondary infections, cytokines commonly associated with innate resistance, TNF alpha, IFN gamma, IL-1 beta and IL-6, were expressed. In contrast, early expression of the genes for IL-2 and IL-2 receptor was detected only during reinfection. Expression was greater in the lungs than in the spleen, attesting to the rapid accumulation of lymphocytes at the infected site. Interestingly, IL-2 mRNA expression declined rapidly and was no longer detectable after 24 h, whereas IL-10 mRNA levels rose sharply during the same period. During reinfection, mRNAs for TNF alpha and IL-6 were 10-fold and for IFN gamma about 50-fold higher than during primary challenge. The results suggest that the pathogenesis of M. pneumoniae diseases may be associated with elevated expression of proinflammatory cytokines.
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PMID:Cytokine gene expression in the lungs of BALB/c mice during primary and secondary intranasal infection with Mycoplasma pneumoniae. 792 Dec 54

Leukocytic cytokines are produced by cells of the immune system and are prominent regulators of the immune response and in some cases various systemic responses. Leukocytic cytokines are released during immune responses and may act in autocrine, paracrine, or endocrine manners. Although over a dozen avian leukocytic cytokines have been described based on functional activities, characterization at the molecular level is not well developed. Two exceptions are 1) myelomonocytic growth factor, a colony-stimulating factor-like cytokine required for the growth and differentiation of hematopoietic precursor cells, particularly myelomonocytic cells; and 2) the avian transforming growth factor-beta (TGF-beta) family of cytokines, which modulate wound healing, bone metabolism, and cellular differentiation. Cytokines with bioactivities similar to mammalian interleukin (IL)-1, IL-2, IL-6, and interferon-gamma have been at least partially purified. Cytokines with bioactivities similar to mammalian IL-8, colony-stimulating factor, and tumor necrosis factor-alpha have been reported but are not well characterized at the molecular level. With a few exceptions, including TGF-beta and thymulin, highly purified leukocytic cytokines of mammalian origin have diminished or no specific activity in avian assay systems. The chicken IL-1 receptor has been cloned and the predicted amino acid sequence shares 60% homology with the human IL-1 receptor. A component of the chicken IL-2 receptor has been partially purified but little is known about other avian leukocytic cytokine receptors. Potential applications of leukocytic cytokines in poultry production originate from their regulation of a variety of functions such as disease resistance, would healing, bone accretion, nutrient partitioning, appetite, growth, and reproduction.
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PMID:Avian leukocytic cytokines. 793 64

IL-2 regulates growth and differentiation of various types of cells in the immune system via its interaction with IL-2 receptor (IL-2R). The high and intermediate-affinity IL-2Rs, which consist of the alpha beta gamma heterotrimer complex and the beta gamma heterodimer complex, respectively, harbor the function of the intracellular signal transduction, indicating that the beta and gamma chains are indispensable for the signal transduction but not the alpha chain. The reconstitution studies of IL-2Rs with alpha, beta and gamma chain genes demonstrated that each subunit has potential for altering the affinity of the receptor, and the cytoplasmic domains of the beta and gamma chains participate in signal transduction in terms of cell growth, activation of alpha tyrosine kinase and enhancement of c-myc, c-fos and c-jun transcription. The region containing the SH2 homologous sequence of the gamma chain should have a critical function for signal transduction. On the other hand, common subunits are known to be shared among receptors for IL-3, IL-5 and GM-CSF, and receptors for IL-6, LIF, OSM and LIF. We have demonstrated that the monoclonal antibody specific for the IL-2R gamma chain completely inhibited not only IL-2-dependent cell growth but also IL-4-dependent, IL-7-dependent, and IL-9-dependent cell growth, suggesting that the gamma chain is possibly shared among receptors for IL-2, IL-4, IL-7 and IL-9. Impairment of the gamma chain function is considered to be closely related to human XSCID characterized by profound T cell defect.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Structure and function of IL-2 receptor subunits]. 802 15


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