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)

Phosphatidylserine (PS) is a necessary cofactor for protein kinase C (PKC) activation, and changes in the synthesis of PS have been shown to participate in the mechanism(s) involved in the transmembrane signaling of interleukin 1 (IL-1). In view of the age-associated defects in T-cell functions, in the present study we have addressed the question of whether an in vivo treatment with PS might interfere with such processes. Furthermore, the effect of an in vitro treatment with PS in human peripheral blood monocytes (PBMC) or splenocytes activated with a lectin mitogen, on the expression of IL-2 receptor, was assessed. While the process of ageing was accompanied by a marked decline of humoral response monitored by anti-BSA antibodies (of the IgG class) production, following immunization with BSA in complete Freund adjuvant, chronic treatment with PS (50 mg/kg, in drinking water), reversed this effect, raising specific antibody titers to levels practically indistinguishable from those measured in young animals. Pharmacological depression of humoral immune response induced by a treatment of adult animals with dexamethasone was similarly reversed by a chronic treatment with PS. While only a pharmacological concentration (10(-5) M) of PS significantly increased IL-2 receptor expression in activated human PBMC, simultaneous treatment of PBMC with inactive doses of PS and the pharmacological activator of PKC (phorbol myristate acetate, PMA, 10(-8) M) resulted in a synergistic stimulation of Tac+ cells. Furthermore, in cultures of rat splenocytes PS (10(-6) M) significantly stimulated the expression of IL-2 receptor, and concomitant addition of PS (10(-7) M) to Con A-stimulated splenocytes produced a significant potentiation of IL-2 receptor induction. The present results indicate that in vivo treatment of ageing animals with the specific phospholipid PS is able to reverse the physiological decline of the humoral immune response induced by the ageing process. Moreover, treatment of young rats with PS reversed the pharmacological associated depression of specific antibody production. The in vitro effects of the phospholipid on human PBMC and rat splenocytes might suggest that PS is implicated in T-cell activation through its action on IL-2 receptor.
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PMID:Phosphatidylserine counteracts physiological and pharmacological suppression of humoral immune response. 239 81

Several T-cell functions are controlled by the regulatory peptide interleukin 2 (IL-2). Binding of IL-2 with specific receptors has been well documented, but the molecular mechanism by which IL-2/IL-2 receptor interaction is transduced is not known. We have found that treatment of IL-2-dependent T-cell lines with IL-2 is followed by a rapid stimulation of inositol phospholipid metabolism, as determined by isotopic methodology employing myo-[1,2-3H]inositol. Increased incorporation of the metabolic precursor into phosphatidylinositol and phosphatidylinositol 4-monophosphate, together with the appearance of radiolabeled phosphatidylinositol 4,5-bisphosphate, occurred within minutes of treatment with IL-2 of factor-dependent CT6 cells. Analysis of labeled water-soluble compounds from prelabeled cells indicated a rapid (within 1 min) stimulation of inositol phospholipid hydrolysis following IL-2 treatment. Increased recovery of [3H] inositol phosphates and appearance of [3H]inositol trisphosphate were observed after treatment with IL-2 of CT6 cells, as well as of a second IL-2-dependent cell line, CTB6. These findings suggests that inositol phospholipid-derived metabolites (i.e. diacylglycerol and inositol trisphosphate) may be part of the mechanism by which certain IL-2 signals are transduced.
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PMID:Interleukin 2 rapidly stimulates synthesis and breakdown of polyphosphoinositides in interleukin 2-dependent, murine T-cell lines. 303 Oct 64

The uptake of free calcium ion (Ca2+) in PHA- or A23187-stimulated lymphocytes was measured using 45CaCl2 and 3H-water. Augmentation of Ca2+ uptake by both mitogens was observed, but the enhanced uptake occurred transiently, sometime within 30 min of the stimulation. The total amount of calcium in quiescent lymphocytes as determined by atomic absorption spectroscopy was about 2.9 X 10(-15) g/cell. When stimulated with PHA, more calcium gradually accumulated in the cells. The maximum amount of accumulation occurred at around 40 h, and was about 2-fold higher than that of control cells. In A23187-stimulated cells, the calcium content increased within 1 h by about 4-fold, reached a maximum at about 6 h (6-fold) and thereafter, surplus calcium was pumped out. The cytosolic free calcium ion concentration (the [Ca2+]i) within single cells was measured using quin 2 or fura-2. The [Ca2+]i was about 1 X 10(-7) M, and a transient increase in the [Ca2+]i was observed in some cells within 1 min after Con A-stimulation. Another rise in the [Ca2+]i was observed around the 40th h, and the maximum expression of the IL-2 receptor was observed at about this time. Therefore the results may indicate that the IL-2-mediated lymphocyte transformation is dependent on the rise in the [Ca2+]i.
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PMID:Calcium ion influx during mitogenic stimulation of lymphocytes. 311 49

The development of oral epithelial expression of Ia antigens and its relationship to the presence of IL-2r+ (CD25+) cells was investigated in rats treated with the water soluble carcinogen 4-nitroquinoline-N-oxide (4NQO). Acetone fixed frozen sections of the palate and tongue were stained using an indirect immunoperoxidase technique and monoclonal antibodies to rat Ia (I-A & I-E) and IL-2 receptor. After 4 weeks 4NQO treatment all rats expressed oral epithelial Ia but thereafter (2-9 months) expression was present in only 20-40% of animals. Epithelial expression of Ia by histologically normal, dysplastic and neoplastic epithelium was always associated with the presence of an underlying inflammatory cell infiltrate containing CD25+ cells. Overall there were significantly more CD25+ cells in tissue specimens containing Ia+ epithelium compared with Ia- epithelium. Furthermore, during the first 4 weeks of carcinogen treatment, a significant positive correlation was found between the CD25+ cell density and occurrence of focal epithelial Ia expression. These results, together with analysis of the T cell, NK cell, macrophage and B cell content of the infiltrates induced by 4NQO, suggest that the CD25+ cells represent activated T cells. Thus, our results in this experimental model are consistent with the idea that epithelial expression of Ia is the result of production of IFN-gamma by locally activated T cells.
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PMID:The relationship between epithelial Ia expression and the inflammatory cell infiltrate during experimental oral carcinogenesis. 314 87

Introduction of 15-30 U of interleukin-2 (IL-2) into the 3rd ventricle of Wistar rats was followed by a marked and significant decrease in neuron discharge frequency in the ventromedial nucleus of hypothalamus and a marked increase in the supraoptic and paraventricular nuclei. The monoclonal antibody ART62 partly blocked these effects. The conventional anti-IL-2 receptor monoclonal antibody ART18 had only a non-significant influence on the effects of IL-2. Since the supraoptic and paraventricular nuclei secrete the antidiuretic hormone, their excitation may offer a partial explanation of the considerable water retention observed during IL-2 therapy against neoplasia.
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PMID:Interleukin 2 modifies the bioelectric activity of some neurosecretory nuclei in the rat hypothalamus. 326 70

The effect of iodine excess on thyroid function and on the immunological sequence of events leading to lymphocytic thyroiditis (LT) was studied in the NB subline of BB/W rats to determine the mechanisms by which the level of iodine intake influences the development of LT in this animal model. Iodine supplemented water (500 micrograms/l, Group 1 or 500 mg/l, Group 2) or non-iodine supplemented tap water (Group 3) was given to breeding pairs and their offspring ad libitum. A Wistar rat group, also given tap water (Group 4) served as controls. To determine the immunological sequence of events, the phenotypic nature of the infiltrating thyroid lymphocytes was examined by specific immunoperoxidase staining in BB/W and Wistar rats at 6, 9, 12, and 15 weeks. Antigen-presenting cells and class II (Ia) antigen expression on thyrocytes were also examined. The first immunological event apparent in the iodine-treated BB/W rats was a sharp increase in the number of Ia positive dendritic cells at 9 weeks compared with control BB/W and Wistar rats. In the iodine excess groups dendritic cells were associated with scattered areas of lymphocytic infiltration, comprising predominantly T helper cells (W3/25). T suppressor cells (OX 8) and IL-2 receptor positive activated T-cells (OX 39) were both present in small numbers. B-cells (OX 12) were absent. In addition, thyrocytes did not exhibit Ia antigen expression. By contrast, lymphocytic infiltration was not found at 9 weeks in control BB/W rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Iodine induced lymphocytic thyroiditis in the BB/W rat: early and late immune phenomena. 832 56

When BALB/c mice were treated with a Kampo (Japanese herbal) medicine "Sho-seiryu-to (SST)" (1 g/kg, 10 times) orally from 7 days before to 5 days after the infection and infected with mouse-adapted influenza virus A/PR/8/34 by nasal-site restricted infection, SST caused increment of the influenza virus hemagglutinin-specific IgA antibody secreting cells in nasal lymphocyte but not in Peyer's patch lymphocyte at 6 days after infection in comparison with water-treated mice. Oral administration of SST also augmented IL-2 receptor beta chain+ (activated) T-cell in Peyer's patch lymphocyte, but not in the nasal lymphocyte. We previously reported that SST showed potent anti-influenza virus activity through augmentation of the antiviral IgA antibody titer in the nasal and broncho-alveolar cavities of the mice (T. Nagai and H. Yamada, 1994, Int. J. Immunopharmacol. 16, 605-613). These results suggest that oral administration of SST shows anti-influenza virus activity in the nasal cavity by activation of T-cell in Peyer's patch lymphocyte and stimulation of production of anti-influenza virus IgA antibody in nasal lymphocyte. When ovalbumin-sensitized allergic pulmonary inflammation model mice were administered orally with SST (1 g/kg) from 8 days before (11 times) or from 2 h after (4 times) to 4 days after the infection and infected with mouse-adapted influenza virus A/PR/8/34, replications of the virus in the both nasal and broncho-alveolar cavities or only nasal cavity were significantly inhibited at 5 days after infection in comparison with water-treated control by augmenting antiviral IgA antibody, respectively. These results suggest that SST is useful for both prophylaxis and treatment of influenza virus infection on patients with allergic pulmonary inflammation, such as bronchial asthma.
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PMID:In vivo anti-influenza virus activity of Kampo (Japanese herbal) medicine "sho-seiryu-to"--stimulation of mucosal immune system and effect on allergic pulmonary inflammation model mice. 965 72

A 4400-bp genomic sequence and a 332-bp truncated cDNA sequence of the interleukin-2 (IL-2) gene of Indian water buffalo (Bubalus bubalis) were amplified by polymerase chain reaction and cloned. The coding sequence of the buffalo IL-2 gene was assembled from the 5' end of the genomic clone and the truncated cDNA clone. This sequence had 98.5% nucleotide identity and 98% amino acid identity with cattle IL-2. Three amino acid substitutions were observed at positions 63, 124 and 135. Comparison of the predicted protein structure of buffalo IL-2 with that of human and cattle IL-2 did not reveal significant differences. The putative amino acids responsible for IL-2 receptor binding were conserved in buffalo, cattle and human IL-2. The amino acid sequence of buffalo IL-2 also showed very high identity with that of other ruminants, indicating functional cross-reactivity.
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PMID:Buffalo (Bubalus bubalis) interleukin-2: sequence analysis reveals high nucleotide and amino acid identity with interleukin-2 of cattle and other ruminants. 1212 Dec 82

Previously we showed that ethanol (EtOH) consumption suppressed IL-2-induced cytolytic activity of murine splenic natural killer (NK) cells. Although IL-2 receptor signaling is involved in activation of NK cells, neither the mechanism for this activation nor the role of EtOH consumption in modulating activation is completely understood. In this study we show by electrophoretic mobility-shift assay (EMSA) that enriched splenic NK cells from EtOH-consuming C57BL/6 mice exhibit reduced NF-kappaB and AP-1 binding activity in response to IL-2 stimulation as compared to the water-drinking mice. Semiquantitative RT-PCR and real-time PCR analyses indicated that EtOH consumption inhibits the induction of perforin, granzyme A, and granzyme B in response to IL-2. Pyrrolidine dithiocarbamate (PDTC) and N-tosyl-L-phenylalanine chloromethyl ketone (TPCK) blocked NFkappaB and AP-1 binding activity in nuclear extracts of IL-2-stimulated NK cells in an EMSA and also inhibited the IL-2-induced expression of perforin, granzyme A, and granzyme B gene expression in enriched NK cells. These inhibitors dramatically suppressed IL-2-stimulated NK cytolytic activity against YAC-1 lymphoma target cells. Taken together, these results suggest that NFkappaB and AP-1 are important regulators of NK cell cytolytic function through regulation of perforin, granzyme A, and granzyme B gene expression. The findings further suggest that the decreased cytolytic activity of IL-2-stimulated NK cytolytic activity in EtOH-consuming mice is due at least in part to impaired transactivation of these and possibly other genes involved in control of NK-cell target lysis.
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PMID:Alcohol consumption decreases IL-2-induced NF-kappaB activity in enriched NK cells from C57BL/6 mice. 1270 Apr 14

A unique process has been developed to convert bituminous coal by controlled wet oxidation followed by base treatment to a water-soluble humate called oxihumate. The effects of oxihumate on the proliferative response of lymphocytes has been studied in vitro and ex vivo. Oxihumate increased the proliferative response of phytohaemagglutinin-stimulated human lymphocytes, from a concentration of 20 microg/ml and upwards. This response was even more striking in the case of lymphocytes from HIV-infected patients and was not limited to the in vitro setting since similar effects were observed ex vivo following administration of a non-toxic dosage of 4 g oxihumate per day to HIV-positive individuals for two weeks. Mechanistic studies revealed that stimulation of the proliferative response of lymphocytes by oxihumate is associated with an increased production of IL-2, as well as expression of the IL-2 receptor in the setting of decreased production of IL-10. Oxihumate therefore holds promise for the treatment of immunocompromized patients.
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PMID:Investigation of the immunostimulatory properties of oxihumate. 1271 Jul 39


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