Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P14784 (IL-2 receptor)
 3,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Previously, using flow cytometric resonance energy transfer and lateral diffusion measurements, we demonstrated that a 95-kDa protein identified by two monoclonal antibodies (OKT27 and OKT27b) interacts physically with the 55-kDa alpha protein of the high-affinity interleukin 2 (IL-2) receptor. In the present study, this 95-kDa protein (p95) was purified and amino acid sequence data were obtained that showed strong homology to the human intercellular adhesion molecule 1 (ICAM-1). The identity of the p95 protein with ICAM-1 was confirmed by sequential immunoprecipitations using OKT27 and an antibody, WEHI-CAM-1, that is directed toward ICAM-1. We confirmed the physical proximity of p95/ICAM-1 to the IL-2 receptor alpha subunit by demonstrating that radiolabeled IL-2 could be cross-linked to this protein expressed on activated T cells. In functional studies, the antibodies OKT27 and OKT27b inhibited T-cell proliferative responses to OKT3, to soluble antigen, and to heterologous cells (mixed lymphocyte reaction). However, these antibodies did not inhibit IL-2-induced proliferation of an IL-2-dependent T-cell line. Taken together with our previous observations, the present studies suggest that ICAM-1 is in proximity and interacts physically with the high-affinity IL-2 receptor. The association of ICAM-1 with the IL-2 receptor may facilitate the paracrine IL-2-mediated stimulation of T cells expressing IL-2 receptors by augmenting homotypic T-T-cell interaction, by receptor-directed focusing of IL-2 release by helper T cells, and by focusing IL-2 receptors of the physically linked cells to the site of lymphocyte function-associated antigen 1-ICAM-1-IL-2 receptor interaction.
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PMID:Association of intercellular adhesion molecule 1 with the multichain high-affinity interleukin 2 receptor. 197 56

Cell surface adhesion molecules (CAM) are important promotors of the immunoinflammatory cascade. The circulating levels of soluble intercellular adhesion molecule 1 (ICAM-1) have previously been shown to correlate with disease activity in inflammatory bowel disease. The primary aim of this study was consequently to investigate if this also applies to mucosal levels of soluble ICAM-1. We measured soluble ICAM-1 levels in intestinal biopsy specimens and the endoscopic activity of 69 patients with ulcerative colitis (UC) and 14 controls and found that the median concentration of soluble ICAM-1 was significantly higher in patients with moderately or very active UC (15.0 ng/ml) as compared to slightly active (9.8 ng/ml) and inactive UC (9.5 ng/ml) as well as controls (6.5 ng/ml) (P < 0.005). To further elucidate the interactions, two other CAM [E-selectin and vascular cellular adhesion molecule 1 (VCAM-1)], together with interleukin-8 (IL-8), IL-2 receptor (IL-2R) alpha and beta chains, were also measured. A significant trend towards higher soluble E-selectin levels in biopsies with active UC (1.8 pg/ml) as compared to inactive UC (1.3 pg/ml) and to controls (< 1.0 pg/ml) (P < 0.01) was also found. In contrast, soluble VCAM-1 was barely detectable in biopsies from two UC patients. A significant correlation was found between soluble ICAM-1 and IL-8 concentrations (r = 0.46; P < 0.0001), and between sICAM-1 and sIL-2R alpha concentrations (r = 0.69; P < 0.0001), while sIL-2R beta was not detected. This study shows that intestinal ICAM-1 and E-selectin correlate with endoscopic activity of UC and with IL-8 and IL-2R alpha levels. These mediators may be useful in monitoring mucosal inflammation in studies exploring the therapeutical potential of targeting CAM. The lack of detectable VCAM-1, which is induced only in venous endothelium is interesting. It may suggest that intestinal inflammation mainly affects arterial endothelial cells and support the theory that intestinal vasculitis is involved in the pathogenesis of inflammatory bowel disease.
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PMID:Increased mucosal concentrations of soluble intercellular adhesion molecule-1 (sICAM-1), sE-selectin, and interleukin-8 in active ulcerative colitis. 879 94

Epstein-Barr virus is associated with several human malignancies including Burkitt's lymphoma, nasopharyngeal carcinoma, and Hodgkin's disease (HD). To examine the effect of Epstein-Barr virus nuclear antigen 1 (EBNA-1) in the pathogenesis of HD, we transfected the gene into the HD cell line L428. EBNA-1 expression was associated with significantly enhanced CD25 expression (interleukin 2 [IL-2]-receptor alpha chain) in transient and stably transfected L428 cells but did not affect the expression of IL-2 receptor beta and gamma chains. There was no up-regulation of the B-cell activation molecules CD23, CD30, CD39, CD40, CD44, CD71, and CD54 (intercellular adhesion molecule 1) or enhanced production of IL-6, IL-10, lymphotoxin alpha, and the soluble form of CD25. Stable EBNA-1-expressing L428 cells were nontumorigenic in SCID mice but showed enhanced lymphoma development in nonobese diabetic-SCID mice compared to mock-transfected cells.
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PMID:Expression of epstein-barr virus nuclear antigen 1 is associated with enhanced expression of CD25 in the Hodgkin cell line L428. 988 70

Our previous data on colorectal cancer suggest that there are faults at the level of mechanisms of the proliferative responses of patients peripheral blood mononuclear cells (PBMC) to the interleukin (IL)-2 and IL-2 PBMC production, which increase with the stage advancement. The damages in the proliferative response seem to be eliminated by the costimulator effects of the signals produced by the anti-CD3 monoclonal antibody (antiCD3), and the disregulation in TH subsets of CD4+ T cells with a malfunction of TH1 cells and an expansion of TH2, might contribute to this situation. So, by using biotherapeutic treatments to allow the generation of productive immune response in these patients it is essential to identify the defect in their immune system to discover how these mechanisms should be appropriately manipulated in vivo to switch their immune response from a non-productive to a productive one. We have studied this in a group of patients and healthy subjects as the control group, performing their immunological evaluation by determining these parameters: serum levels of IL-2, interferon (IFN) gamma, IL-4, IL-6, IL-7, IL-8, tumour necrosis factor (TNF) alpha, soluble IL-2 receptor (sIL-2R), intercellular adhesion molecule 1 (sICAM-1) and CD30 (sCD30) molecules; PBMC phenotypic antigens expression (CD3, CD4, CD8, CD19, CD16, CD56, CD57, CD25) on peripheral blood mononuclear cells (PBMC); proliferative response of PBMC to IL-2, IL-4 and anti-CD3 monoclonal antibody (antiCD3). Moreover, since mutant c-Ki-ras oncogene is a very frequent finding in colorectal cancers and there are indications which suggest its involvement in tumour progression, the analysis of c-ki-ras codon 12 and 13 were determined and the statistical evaluation of the above immunological parameters were performed by comparing the patient groups with (M+) and without (M-) these mutations with each other, and with the healthy group. The results underline the necessity of biotherapeutic treatments inducing TH1 cell functions in these patients. Moreover in M+ it seems also important to solve the problem of the switch from B to macrophage cells as immune cells which present antigens, and the possible involvement of c-Ki-ras gene mutations in the impairment of T cell receptor activation (TCR).
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PMID:Necessity of biotherapeutic treatments inducing TH1 cell functions in colorectal cancer. 1085 98