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 large number of laboratory tests have been developed within the past decade to measure factors involved in the immune inflammation of RA. These can be divided into genetic markers, general measures of inflammation, autoantibodies and tissue-specific markers. In general, it is simpler to prove the power of a certain test to measure the disease process than to predict outcome. Apart from RF positivity and CRP/ESR, few, if any, tests have proven to be of importance in independent studies from different centres. Among the promising candidates for future work are detailed analysis of the HLA-D region genes, sulphoxidation status, the autoantibody against RA33 nuclear antigen, soluble IL-2 receptor measuring lymphocyte activity, hyaluronate/hyaluronan or PIIINP from synovial tissue, the combined use of COMP and proteoglycan epitope tests for cartilage matrix, and pyrodinoline cross-linking for collagen from bone and cartilage. The ideal setting for testing such markers are prospective cohort studies starting early in the disease, and since many such studies have been initiated recently, one can expect much new information in coming years. Attention needs to be devoted to the kinetics of marker metabolism, since many are degraded or removed at very fast rates from the circulation, making serum assays less informative.
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PMID:The search for laboratory measures of outcome in rheumatoid arthritis. 137 45

Schistosomiasis causes pathology in an estimated 200 million individuals. Clinical disease is caused by a complex immunopathologic response to the parasite ova, which are deposited in the host tissues. This immunopathologic response is caused by T lymphocytes which express the high-affinity IL-2 receptor (IL-2R). DAB389IL-2 is a diphtheria toxin-IL-2 fusion toxin protein which functionally inactivates or kills cells which bear the high-affinity IL-2R. DAB389IL-2 has been used in man to suppress IL-2R-dependent immune reactivity. Therefore, we reasoned that DAB389IL-2 might suppress immunopathology in schistosomiasis. In these studies we assessed the in vitro and in vivo effects of DAB389IL-2 on the development of immunopathology in murine schistosomiasis. DAB389IL-2 suppressed IL-2, lectin mitogen (Con A), and soluble Schistosoma mansoni egg antigen-induced lymphocyte proliferation and in vitro granuloma formation. In addition, DA-B389IL-2 suppressed in vitro IL-2R expression. DA-B389IL-2 also suppressed the development of granulomas and collagen deposition in vivo in the livers of infected animals. Therefore, DAB389IL-2 may have potential for the targeted reduction of immunopathology due to schistosomiasis in man.
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PMID:Suppression of immunopathology in schistosomiasis by interleukin-2-targeted fusion toxin, DAB389IL-2. I. Studies of in vitro and in vivo efficacy. 749 23

Recombinant interleukin (IL)-15, derived from a simian kidney epithelial cell line, is a chemoattractant for human blood T lymphocytes judged by its ability to increase the proportion of cells in polarized morphology, to stimulate invasion of collagen gels containing IL-15, and to increase the proportion of locomotor cells observed by time-lapse videorecording. The ability of lymphocytes to respond was partly, but not completely, inhibited by pretreatment with anti-IL-2 receptor beta-chain. The activity of IL-15 was completely abolished by preincubation with aIL-15 but unaffected by preincubation with aIL-2. No response of monocytes, neutrophils, or B lymphocytes to IL-15 was observed.
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PMID:Chemoattraction of human blood T lymphocytes by interleukin-15. 786 44

Recombinant human interleukin-2 (IL-2) stimulated locomotion and chemotaxis of human blood lymphocytes as measured by shape change to a polar morphology, by orientation in a chemotactic gradient, and by a collagen gel invasion assays. IL-2 stimulated locomotion of a larger number of lymphocytes than IL-8 or macrophage inflammatory protein (MIP)-1 alpha, but the maximally effective concentration of all three was similar (around 100 ng/ml). Activation of the lymphocytes by culture for 24-48 hr in fetal calf serum (FCS), anti-CD3, or purified protein derivative (PPD) increased the proportion of responsive cells, though even direct from blood, > 20% of lymphocytes showed locomotor responses to IL-2, a figure which was similar to the number of IL-2 receptor (IL-2R) beta+ lymphocytes but higher than the number of IL-2R alpha+ cells. The effect of antibodies to IL-2R alpha and IL-2R beta as inhibitors of these responses was therefore tested. Anti-IL-2R beta (alpha IL-2R beta) completely inhibited the response of both resting and activated cells: alpha IL-2R alpha had no inhibitory effect on the locomotion of lymphocytes direct from blood, and only partially inhibited locomotion after culture for 48 hr in alpha CD3 or PPD. The locomotor response to IL-2 was inhibited by pretreatment of the cells with herbimycin, a protein tyrosine kinase (PTK) inhibitor, an observation consistent with PTK control of cytoskeletal activity following binding of IL-2 to IL-2R beta. These results suggest that the beta-chain of the IL-2R is required for activation of lymphocyte locomotion by IL-2 and that binding of IL-2 to this chain alone is sufficient for a response.
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PMID:Chemoattractant activity of IL-2 for human lymphocytes: a requirement for the IL-2 receptor beta-chain. 804 89

Topical cyclosporin A is increasingly being used in the treatment of ocular surface immune-mediated disorders. The availability of the drug in oil-based vehicles or collagen shields has restricted its use because of ocular irritation or blurring of vision. Although topical cyclosporin is being used more frequently, its effect on the immunocompetent cells of the conjunctiva is not known. Our aim was to study the effect of cyclosporin instillation on the immunocomponent cells of conjunctiva-associated lymphoid tissue (CALT) of Lewis rat, using a novel method of topical drug delivery. A suspension of collagen bits impregnated with cyclosporin A was instilled into eyes of Lewis rats for 4 days (group 1) or 8 days (group 2). Control rats (group 3) received the suspension without cyclosporin. Frozen sections of eyelids and conjunctiva were immunostained with the following monoclonal antibody markers: W3/13 (CD3), W3/25 (CD4, macrophages), OX-8 (CD8), MARD-3 (B cells), ED1, ED2 (macro/monocytes), OX-6 (class II MHC, Ia) and OX-39 (CD25, IL-2 receptor). Intraepithelial (IE) and substantia propria cells for each subset were counted and expressed as numbers per section. By day 8, intraepithelial and substantia propria cells for all the above markers, except B cells, showed a significant reduction in numbers. The p values were < 0.02 for W3/13 (CD3), W3/25 (CD4), OX-8 (CD8), OX-39 (CD25) (IE only), ED1, ED2 and OX-6 positive cells. Goblet cells of control animals showed strong positive reaction with OX-39 (CD25) antibody. This was completely abolished following 8 days of topical cyclosporin. This study demonstrated that topical cyclosporin A induces a marked reduction in numbers of all subtypes of immunocompetent cells in the conjunctival epithelium and substantia propria.
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PMID:The effect of topical cyclosporin on conjunctiva-associated lymphoid tissue (CALT). 894 92

1. Staphylococcal enterotoxine B (SEB; superantigen) accelerated the onset of arthritis in mice preimmunized with type II collagen (SEB-potentiated collagen-induced arthritis). Cyclosporin A and FK-506 inhibited the induction and development of clinical signs and histopathological changes of SEB-potentiated collagen-induced arthritis in mice. 2. Simultaneously, both cyclosporin A and FK-506 inhibited the development of humoral and cellular immunity to type II collagen. 3. The expression of IL-2 receptor (CD25) by SEB on splenocyte T cells from collagen-preimmunized mice was inhibited by both agents in ex vivo experimentation.
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PMID:Cyclosporin A and FK-506 inhibit development of superantigen-potentiated collagen-induced arthritis in mice. 955 34

A 70-year-old man was referred to our hospital in March 2001 for the purpose of evaluation for anemia and thrombocytopenia. Physical examination revealed hepatosplenomegaly, normal skin, and normal neurologic findings. Blood examination showed a white blood cell count of 10,900/microliter, with a differential count of 58.5% eosinophils and 3.5% blast cells. Flow cytometric analysis of eosinophils revealed that they were positive for CD33, CD13, CD25, and HLA-DR. Bone marrow aspiration could not be performed due to dry tap, and bone marrow core biopsy specimen revealed severe myelofibrosis with blastoid cells proliferation. Cytogenetic analysis of bone marrow cells showed isochromosome 17. FISH analysis using a RAR alpha probe (17q21.1) demonstrated 62% of peripheral blood nucleated cells having three signals. BCR/ABL gene rearrangement by FISH analysis was not observed. Allergic disease, infectious disease, parasitic disease, collagen vascular diseases, pulmonary disease, and neoplastic disorders were excluded. Therefore, a diagnosis of chronic eosinophilic leukemia was made. The patient had no symptoms of hypereosinophilia. However, eosinophils with sparse granulation, positivity for CD25, elevated serum levels of soluble IL-2 receptor, and elevated serum levels of eosinophil cationic protein suggested activation of eosinophils. Further analysis is needed regarding the activation of eosinophils in chronic eosinophilic leukemia.
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PMID:[CD25 positive chronic eosinophilic leukemia with myelofibrosis]. 1246 27

There is little information available regarding the role of inflammatory cells and cytokines in the pancreatic tissue during acute interstitial pancreatitis. The single intravenous application of dibutyltin dichloride (DBTC) induces a pancreatitis in rats with a dosage dependent course. We analyzed the infiltrating leukocytes and the cytokine expression profile in the experimental model of DBTC-initiated mild interstitial pancreatitis during a time course of 4 weeks. Macrophages dominated among the infiltrating inflammatory cells detected by immunohistochemistry. The expression of IL-1beta, IL-10, and TGFbeta1 was shown to be elevated 24 hours after onset of pancreatitis reaching a maximum during the first week. Positive immunostaining of IL-1beta, IL-10, or TGFbeta1 was not restricted to infiltrating leukocytes but was found to various degrees in pancreatic cells. Transcripts of collagen type 1 reached high levels in the first week, but were down regulated thereafter. There was no significant expression of IL-2, IL-2 receptor, IL-4, TNFalpha, or IFNgamma. Our data show that the experimental interstitial pancreatitis was characterized by macrophage infiltration accompanied by elevated cytokine expression that lasted longer than the visible morphologic lesions. These inflammatory processes might create the environment that makes the pancreas more susceptible to further damaging effects.
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PMID:Immunologic characterization of acute pancreatitis in rats induced by dibutyltin dichloride (DBTC). 1282 12

Tumor endothelial marker 8 (TEM8) is induced in tumor-associated vasculature and acts as a receptor for Protective Antigen (PA), the cell-binding component of the anthrax toxin determinant for toxin entrance into cells. However, the normal function for TEM8 remains unknown. We show that TEM8 functions as an adhesion molecule mediating cell spreading on immobilized PA and collagen I. The mechanism for TEM8 interaction with collagen I was cell type-specific, because binding to collagen I was abrogated by beta1 integrin function blocking antibody in HEK293 cells, but not in primary synovial rabbit fibroblasts. Binding to PA remained unaffected by the addition of beta1 integrin function blocking antibody. Whereas the extracellular and transmembrane domains of TEM8 were sufficient to provide cell attachment, the intracellular domain was critical for spreading. Fusion of the cytosolic domain of TEM8 to the IL-2 receptor, conferred cell-spreading capability on IL-2 receptor antibody substrates. The cytoplasmic domain mediated linkage with the actin cytoskeleton as it co-precipitated actin and determined partitioning of TEM8 to the actin-containing detergent insoluble cellular fraction. TEM8 anchorage to actin was relevant as spreading was inhibited by the cytoskeleton-disrupting drug cytochalasin D, but persisted in the presence of the microtubule-depolymerizing drug nocodazole, and in cells lacking intermediate filaments. Thus, our results indicate that TEM8 is a new adhesion molecule linking collagen I or PA to the actin cytoskeleton.
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PMID:Anthrax toxin receptor 1/tumor endothelium marker 8 mediates cell spreading by coupling extracellular ligands to the actin cytoskeleton. 1676 26

The performance of a chemical luminescence test reagent "Immulyze IL-2R II" with an automated immune chemiluminescent system "IMMULITE 2000XPi" for the measurement of serum soluble IL-2 receptor in clinical samples was investigated. The satisfactory results were obtained for the reproducibility, precision, linearity, and sensitivity, and no interference with hemolysis, bilirubin, chyle or intrafat was observed. A significant correlation was found between the values of sIL-2R measured by the Cell-free N IL-2R and those obtained by the IMMULYZE IL-2R II. The measurements were stable regardless of the methods of sample preservation, or repeated freeze-thawing procedures. Elevated concentrations of sIL-2R over 1,000 U/mL were found in multiple types of collagen diseases or severe cases of allergic diseases, indicative that sIL-2R levels might correlate with the severity of autoimmune diseases. In patients with lymphoma, sIL-2R levels correlated with the lactate dehydrogenase (LD) activity. Among the lymphoma cases with sIL-2R levels over 1,000 U/mL, the majority (84%) had significantly higher levels of LD, and among them, 81% were at the clinical stage IV. We observed that sIL-2R levels increased from the early stages of lymphoma, while LD activities increased at the advanced stages. Our present findings suggest that sIL-2R is a promising marker for the diagnosis of autoimmune and allergic diseases, and also for the diagnosis and staging of lymphomas.
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PMID:[The performance of the automated immune chemiluminescent system "IMMULITE 2000XPi for the measurement of serum soluble IL-2 receptor in clinical samples]. 2277 70


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