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)

Five opioid peptides (alpha-, beta-, and gamma-endorphin, methionine- and leucine-enkephalin) were tested for their effect on the concanavalin A-induced proliferative response of splenocytes of adult male F344 rats. The continuous presence of these opioid peptides during culture of T cells did not affect proliferation. However, 30 min of preincubation with beta-endorphin (beta-end), but not with the other opioid peptides, resulted in a dose-dependent enhancement of proliferation of 50-100%. This potentiating effect of beta-end on proliferation was preceded by an increase in the production of interleukin-2 (IL-2) and in the extent of IL-2 receptor expression. The stimulatory effect of beta-end was not prevented by naloxone, indicating that classical opioid receptors were not involved. The continuous presence of beta-end (or alpha-end) in cultures of cells that had been preincubated with beta-end completely abolished the stimulatory effect, pointing towards the potential of beta-end to regulate T-cell function via different mechanisms.
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PMID:Two opposing modes of action of beta-endorphin on lymphocyte function. 203 14

Endogenous opioids exert a variety of extra central nervous system (CNS) functions, including modulation of some human lymphocyte functions. The latter opioid activity may result in elevation of human natural killer (NK) function (i.e. by beta-endorphin), which is reversed by an opioid antagonist, Naloxone. Since recent evidence has suggested both structural and functional similarities between lymphokines known to elevate human NK function (interferon and interleukin-2) and endogenous opioids, we investigated if Naloxone could modulate lymphokine-enhanced human NK activity. Naloxone blunted, in a dose-dependent fashion, the NK-enhancing activity of peripheral blood lymphocytes or large granular lymphocytes by recombinant interferon-alpha (IFN-alpha) or interleukin-2 (IL-2). Naloxone decreased the uptake of radiolabelled IL-2 receptors. beta-endorphin also decreased the binding of radiolabelled IL-2 or IL-2 receptor-positive human lymphocytes. Finally, labelled Naloxone was inhibited from binding to phytohaemagglutinin (PHA)-stimulated lymphocytes by either beta-endorphin or IL-2. These findings strongly suggest that human lymphocyte receptors for opioid, IFN or IL-2 molecules, once occupied, have distinct influences on the alternate receptor. In addition, these data further strengthen the potential role of CNS-mediated influences on the human immune system.
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PMID:Interaction between endogenous opioids and IL-2 on PHA-stimulated human lymphocytes. 239 65

Pituitary cells were shown to release corticotropin (ACTH) in response to interleukin-2 (IL-2) and to express a protein that is related to the alpha-chain of the IL-2 receptor (IL-2R). The alpha-chain-like molecule was bound by a rat monoclonal antibody to the murine IL-2 receptor as well as to IL-2. Sodium dodecylsulfate-polyacrylamide gel electrophoretic analysis of the affinity-purified material from pituitary cells demonstrated a protein which was similar to that which was isolated from activated splenocytes. Thus, IL-2 and its receptor may be one of several hormone-receptor pairs utilized by both the immune and neuroendocrine systems for intersystem communication.
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PMID:Interleukin-2 induction of ACTH secretion: presence of an interleukin-2 receptor alpha-chain-like molecule on pituitary cells. 253 95

There has been considerable effort in chemically conjugating a variety of plant and bacterial toxins to monoclonal antibodies that are directed to surface antigens on target cells. Coupling has been mediated through disulfide linkage, and the resulting conjugates are known generically as immunotoxins. In general, there are a few shortfalls to this approach. For example, since it is clear that not all surface antigens are internalized, one cannot predict the fate of a given IT once bound to its determinant on the surface of a target cell. In addition, in most instances one must activate the amino moiety of lysine residues with a heterobifunctional reagent in order to form disulfide linkage between the ligand and toxophore components. Since the number of reactive groups may be large, the disulfide linked conjugate molecules most likely represent a family of isomeric molecules rather than a defined protein. As a result, one cannot readily manipulate the fine structure of an IT in order to probe the mechanism of toxophore entry into the target cell. The approach that our group has taken toward the development of targeted cytotoxins, however, differs in a fundamental way: Rather than chemically coupling the ligand with toxophore through a disulfide bond, we have turned to genetic engineering in order to create gene fusions whose chimeric products are joined through a peptide bond. Thus, we have genetically constructed a family of fusion genes in which the receptor binding domain of diphtheria toxin has been deleted and replaced with DNAs encoding either alpha-MSH or IL-2. In each instance, it was known that the polypeptide ligand component of the fusion protein bound to specific receptors on target cells and was internalized by receptor mediated endocytosis. We reasoned, therefore, that the substitution of the diphtheria toxin receptor binding domain by these ligands should result in the formation of 'new' toxins whose action should be targeted toward selected eukaryotic cells that expressed either the alpha-MSH or IL-2 receptor. As along as the ligand component was exposed on the surface of the chimeric toxin, the molecule should bind to its receptor and be drawn into the cell by receptor-mediated endocytosis. Since the toxin-related/peptide hormone fusion protein is the product of a chimeric gene, it is a single molecular species. This has allowed us to begin to probe by site-directed mutagenesis the structure of fragment B sequences that are required to facilitate the translocation of fragment A across the target cell membrane.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Diphtheria-related peptide hormone gene fusions: a molecular genetic approach to chimeric toxin development. 290 22

The effects of long-term corticotropin-releasing hormone (CRH) infusion in the lateral ventricle of the rat on hypothalamic-pituitary-adrenocortical (HPA) axis parameters and on the immune system function were studied. Compared with infusion of vehicle, the CRH treatment produced a sustained overactivity of the HPA axis, as evidenced by elevated plasma ACTH and corticosterone levels, increased anterior pituitary POMC messenger RNA (mRNA) expression, and adrenal enlargement. Long-term CRH treatment also inhibited body weight gain and reduced thymus and spleen weight. In the CRH-treated animals, both Concanavalin A (Con A)-induced T lymphocyte proliferation and lipopolysaccharide (LPS)-induced B lymphocyte mitogenesis was largely suppressed. Surprisingly, interleukin-2 (IL-2) levels were higher in supernatants of splenocyte cultures from CRH-treated rats than in those of control animals. However, IL-2 receptor alpha chain (IL-2R alpha) mRNA expression after Con A stimulation was highly suppressed in the CRH-treated animals. In addition, Northern blot analysis of RNA from splenocytes isolated from spleens of CRH-treated rats revealed a marked expression of IL-1 beta mRNA, in contrast to the barely detectable levels of this cytokine in control animals. Moreover, incubation of total splenocytes and spleen macrophages with LPS resulted in an enhanced induction of IL-1 beta mRNA in cells of CRH-treated rats compared with that of control animals. When adrenalectomized rats were treated with CRH or vehicle, the effects of the CRH treatment on T and B cell proliferation, IL-2 production, and IL-1 beta mRNA expression were abolished. Thus, a continuously increased HPA axis drive results in disparate changes in immune system function. Whether the observed changes in cytokine expression should be regarded as physiologically adaptive adjustments in support of immune function or as potentially pathological anomalies remains to be elucidated.
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PMID:Long-term intracerebroventricular corticotropin-releasing hormone administration induces distinct changes in rat splenocyte activation and cytokine expression. 775 Apr 92

Interleukin-2 (IL-2)-like immunoreactivity and IL-2 receptor immunoreactivity have been reported in different brain regions, under normal and pathophysiological conditions. IL-2 stimulates hypothalamic corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) release and that of pituitary adrenocorticotropin. The amygdala, known to contain high levels of CRF, is involved in stress-related reactions, including regulation of the hypothalamo-pituitary-adrenal axis. IL-2 will release AVP from both the hypothalamus and the amygdala, which further supports a role for cytokine effects in the amygdala in neuroimmune interactions. In the present study, we compared the effects of IL-2, acetylcholine and norepinephrine on the in vitro release of CRF from the amygdala or hypothalamus. In addition, we used these release systems to evaluate the possible involvement of nitric oxide (NO)-mediated signaling in CRF release. IL-2 stimulates CRF release in both regions, in a calcium- and dose-dependent manner. Nitroprusside, an NO generator, also induces CRF release. This IL-2-induced CRF release is antagonized by Ng-methyl-L-arginine and hemoglobin, known NO antagonists. Finally, norepinephrine and acetylcholine induce CRF release. The norepinephrine-induced CRF release is antagonized by phentolamine and propanolol and the acetylcholine-induced release by atropine and mecamylamine, which suggests the involvement of both alpha and beta adrenergic receptors and both muscarinic and nicotinic receptors. The acetylcholine-induced CRF release is antagonized by Ng-methyl-L-arginine, but the norepinephrine-induced response is not. These data support the suggestion that the amygdala may participate in communications between the neuroendocrine and immune systems.
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PMID:Interleukin-2 (IL-2) induces corticotropin-releasing factor (CRF) release from the amygdala and involves a nitric oxide-mediated signaling; comparison with the hypothalamic response. 785 99

A somnogenic function is suspected for various cytokines. Foregoing experiments in humans indicated a selective increase in the production of interleukin-2 (IL-2) during sleep as compared with nocturnal wakefulness. Here, we examined whether conversely, IL-2 exerts a promoting influence on sleep. Also, the effects of IL-2 administered at ultra-low doses on systemic immune and endocrine parameters were assessed. Eighteen healthy men participated in three night sessions, receiving subcutaneously at 19:00 h either placebo or recombinant human IL-2 at doses of 1000 and 10,000 IU/kg bw. Polysomnographical recordings were obtained between 23:00 and 07:00 h. Blood was collected repeatedly to determine (i) white blood cell (WBC) counts including the enumeration of monocytes, natural killer (NK) cells, and lymphocyte subsets, (ii) serum concentrations of IL-2, soluble IL-2 receptor (sIL-2r), IL-4, IL-6, and interferon-gamma (IFN-gamma), and (iii) concentrations of adrenocorticotropin (ACTH), cortisol, thyreotropin (TSH), and growth hormone (GH). Changes after 1000 IU/kg bw IL-2 generally remained non-significant. However, distinct effects occurred after 10,000 IU/kg bw IL-2, inducing serum IL-2 concentrations selectively activating the high affinity IL-2 receptor. At this dose, IL-2 reduced the number of circulating lymphocytes (including all major subtypes) and NK cells, while counts of monocytes and neutrophils were increased. IL-4 release was stimulated and IFN-gamma concentration reduced after IL-2. Also, IL-2 increased the TSH concentration. There were no hints at a sleep promoting effect of IL-2. Immune changes suggest that nocturnal IL-2 administration induces a shift towards Th2 mediated defense.
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PMID:Systemic immune parameters and sleep after ultra-low dose administration of IL-2 in healthy men. 1248 Apr 97