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Identification of a direct interaction between interleukin 2 and the p64 interleukin 2 receptor gamma chain.

Voss, S D; Leary, T P; Sondel, P M; Robb, R J
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 15/03/1993 Português
Relevância na Pesquisa
65.88%
The interleukin 2 receptor (IL-2R) consists of at least two subunits, alpha and beta, both of which can bind interleukin 2 (IL-2). Recent studies have demonstrated the existence of a third subunit, a 64-kDa molecule termed IL-2R gamma chain, and have suggested that gamma chain functions to regulate the rate of IL-2 dissociation from the receptor. In the present report we have addressed whether the gamma chain modulates IL-2R affinity by contributing contact sites for IL-2 binding. Using reagents that allow the IL-2R complex to be immunoprecipitated through the IL-2 molecule itself, we demonstrate the existence of a stable IL-2-IL-2R gamma-chain complex. These studies thus establish that the IL-2R gamma chain directly contributes to the IL-2-binding site, consistent with the hypothesis that gamma chain influences IL-2R affinity through its direct interaction with IL-2.

Identification of specific residues of human interleukin 2 that affect binding to the 70-kDa subunit (p70) of the interleukin 2 receptor.

Collins, L; Tsien, W H; Seals, C; Hakimi, J; Weber, D; Bailon, P; Hoskings, J; Greene, W C; Toome, V; Ju, G
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /10/1988 Português
Relevância na Pesquisa
65.91%
Analogs of interleukin 2 containing defined amino acid substitutions and deletions were assayed for bioactivity and for competitive binding to the high-affinity human interleukin 2 receptor complex and its two component subunits, a 55-kDa subunit (p55 or TAC) and a 70-kDa subunit (p70). Substitution of Asp20 or deletion of Phe124 resulted in inactive analog proteins that were unable to interact with the high-affinity p55/p70 complex or the intermediate-affinity p70 subunit of the interleukin 2 receptor. These analogs, however, retained the capacity to compete for binding to the low-affinity p55 subunit. The presence of the carboxylic acid in the side chain of Asp20 was necessary for effective binding to the p70 protein. In contrast, substitution of Trp121 and Leu17 created analogs that were inactive in the bioassay and all three binding assays. The effects of these mutations on protein conformation were assessed by circular dichroism. These results demonstrate that specific residues in the NH2 and COOH termini of interleukin 2 are crucial for its structure and activity.

Dexamethasone inhibits human interleukin 2 but not interleukin 2 receptor gene expression in vitro at the level of nuclear transcription.

Boumpas, D T; Anastassiou, E D; Older, S A; Tsokos, G C; Nelson, D L; Balow, J E
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /05/1991 Português
Relevância na Pesquisa
65.85%
Glucocorticosteroids have an inhibitory effect on the expression of interleukin 2 (IL-2) and interleukin 2 receptor (IL-2R) genes. To determine the mechanisms of this inhibition, human T lymphocytes were stimulated with mitogens in the presence of dexamethasone. Nuclear transcription run-off assays showed that high doses of dexamethasone inhibited the transcription of the IL-2 gene but not that of the IL-2R gene. Post-transcriptionally, high doses of dexamethasone (10(-4) M) were required to inhibit IL-2R mRNA levels by 50%, whereas lower doses (10(-6) M) inhibited by greater than 70% the accumulation of IL-2 mRNA. IL-2 mRNA half-life decreased in the presence of dexamethasone (10(-6) M) by approximately 50%. At the protein product level, dexamethasone inhibited both IL-2 production, as well as cell surface and soluble forms of IL-2R. IL-2R gene expression was inhibited for at least 72 h after exposure of cells to dexamethasone. In the presence of exogenous IL-2, dexamethasone failed to exert a significant effect on the production of IL-2R protein. These data indicate that dexamethasone has a greater effect on the expression of the IL-2 gene than on the IL-2R gene. Dexamethasone both inhibits transcription of the IL-2 gene and decreases the stability of IL-2 mRNA. The effect of dexamethasone on the IL-2R gene is post-transcriptional and may result indirectly from decreased IL-2 production.

Expression of Tac antigen component of bovine interleukin-2 receptor in different leukocyte populations infected with Theileria parva or Theileria annulata.

Dobbelaere, D A; Prospero, T D; Roditi, I J; Kelke, C; Baumann, I; Eichhorn, M; Williams, R O; Ahmed, J S; Baldwin, C L; Clevers, H
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /12/1990 Português
Relevância na Pesquisa
65.91%
The Tac antigen component of the bovine interleukin-2 receptor was expressed as a Cro-beta-galactosidase fusion protein in Escherichia coli and used to raise antibodies in rabbits. These antibodies were used for flow cytofluorimetric analysis to investigate the expression of Tac antigen in a variety of Theileria parva-infected cell lines and also in three Theileria annulata-infected cell lines. Cells expressing Tac antigen on their surface were found in all T. parva-infected cell lines tested whether these were of T- or B-cell origin. T cells expressing Tac antigen could be CD4- CD8-, CD4+ CD8-, CD4- CD8+, or CD4+ CD8+. Tac antigen expression was observed both in cultures which had been maintained in the laboratory for several years and in transformed cell lines which had recently been established by infection of lymphocytes in vitro with T. parva. Northern (RNA) blot analysis demonstrated Tac antigen transcripts in RNA isolated from all T. parva-infected cell lines. Three T. annulata-infected cell lines which were not of T-cell origin were also tested. Two of them expressed Tac antigen on their surface. Abundant Tac antigen mRNA was detected in these T. annulata-infected cell lines, but only trace amounts were demonstrated in the third cell line...

Interleukin-1 alpha, soluble interleukin-2 receptor, and IgG concentrations in cystic fibrosis treated with prednisolone.

Greally, P; Hussain, M J; Vergani, D; Price, J F
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /07/1994 Português
Relevância na Pesquisa
65.86%
The cytokines interleukin-1 and interleukin-2 participate in the inflammatory response, and may contribute to hypergammaglobulinaemia G and the development of lung injury in cystic fibrosis. Anti-inflammatory treatment with corticosteroids may attenuate this response. The effect of a 12 week course of oral prednisolone on spirometry and serum concentrations of interleukin-1 alpha (IL-1 alpha), soluble interleukin-2 receptor (sIL-2R), and IgG was investigated in 24 children with cystic fibrosis. Prednisolone was administered, in a double blind and placebo controlled manner, at an initial dose of 2 mg/kg daily for 14 days and tapered to 1 mg/kg on alternate days for 10 weeks. The treated group (n = 12) experienced an increase in forced expiratory volume in one second and forced vital capacity at 14 days, however, these changes were smaller at 12 weeks. In the treated group, change in pulmonary function was associated with decreased serum IgG and cytokine concentrations. Prednisolone suppresses serum concentrations of these cytokines, which may participate in the inflammatory response, the excessive synthesis of IgG, and airflow obstruction observed in cystic fibrosis patients.

Immunohistochemical changes in the jejunum in first degree relatives of patients with coeliac disease and the coeliac disease marker DQ genes. HLA class II antigen expression, interleukin-2 receptor positive cells and dividing crypt cells.

Holm, K; Savilahti, E; Koskimies, S; Lipsanen, V; Mäki, M
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /01/1994 Português
Relevância na Pesquisa
65.86%
The staining of HLA class II antigens, the presence of cells positive for interleukin-2 receptors, the proportion of crypt cells in mitosis in the jejunal biopsy specimens, and the dose of coeliac disease marker HLA-DQ genes were studied in 75 healthy family members of coeliac disease patients. Eleven had silent coeliac disease; in the rest the morphology of the jejunum was normal. In the specimens from family members, staining of epithelial cells with HLA-DP and -DR antibodies was more widely distributed and stronger than in those from 19 controls. Interleukin-2 receptor+ cells were seen in the epithelium of all eight specimens from subjects with silent coeliac disease, and also in 24 morphologically normal specimens from family members, but not in the 19 control specimens. The proportion of crypt cells in mitosis was increased only in the specimens from the subjects with silent coeliac disease. The staining intensity of the epithelial cells with HLA-DP and -DR antibodies, the presence of interleukin-2 receptor+ cells and the percentage of crypt cells in mitosis were significantly associated with the number of coeliac disease marker DQB genes. Many family members of patients with coeliac disease have signs of inflammation even in morphologically normal jejunum; these inflammatory changes together with coeliac disease marker DQ genes may point to latent disease in these subjects.

The monocyte interleukin-2 receptor light chain: production of cell-associated and soluble interleukin-2 receptor by monocytes.

Kniep, E M; Strelow, I; Lohmann-Matthes, M L
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /02/1992 Português
Relevância na Pesquisa
65.86%
Stimulation with lipopolysaccharide (LPS) initiated monocytes to produce interleukin-2 receptor light chain (p55 IL-2R). After stimulation with LPS for 48 hr, considerable quantities of soluble IL-2R were found in the supernatants of monocytes, exceeding even the amount of soluble IL-2R produced by activated T lymphocytes. Cell-associated p55 IL-2R was also increased during the first 24 hr of stimulation, after which time it remained constant. Fractionation of cells and analysis of cytoplasm, mitochondria, plasma membranes and nuclei for the presence of p55 IL-2R revealed that the main portion of receptor was present in the cytoplasm. This led to the conclusion that in monocytes cell-associated p55 IL-2R is not necessarily attached to membranes but is present in a soluble form in the cytoplasm, presumably freshly produced with the aim of being secreted. Stimulation of monocytes with pure recombinant interferon-gamma did not lead to augmentation of p55 IL-2R, as shown by enzyme-linked immunosorbent assay, binding of antibodies directed against the receptor (anti-Tac, CD25) and analysis of p55 IL-2R gene expression.

Soluble interleukin-2 receptor, interleukin-2 and interleukin-4 in sera and supernatants from patients with progressive systemic sclerosis.

Famularo, G; Procopio, A; Giacomelli, R; Danese, C; Sacchetti, S; Perego, M A; Santoni, A; Tonietti, G
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /09/1990 Português
Relevância na Pesquisa
65.88%
We studied the sera of patients with progressive systemic sclerosis (PSS) for elevated levels of soluble interleukin-2 receptor (sIL-2R), interleukin-2 (IL-2) and interleukin-4 (IL-4). We also measured IL-2, IL-4 and B cell growth factor (BCGF) activity in supernatants of peripheral blood mononuclear cells from the same patients. The finding of elevated serum sIL-2R and IL-2, and the increased levels of IL-2, IL-4 and BCGF activity in culture supernatants indicates that T lymphocyte hyperactivity likely play a major role in PSS. The failure to detect under our experimental conditions a direct proliferative effect of recombinant IL-2 on enriched normal B cells might suggest that IL-4 is the cytokine mainly responsible of the BCGF activity recovered in PSS supernatants.

Interleukin 2 receptor expression by human blood lymphocytes after vaccination with pneumococcal polysaccharides.

Tvede, N; Heilmann, C; Christensen, L D
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /06/1989 Português
Relevância na Pesquisa
65.85%
Proliferative responses of unseparated peripheral blood mononuclear cells (PBMC) and blood T cells to recombinant interleukin 2 (rIL-2) were significantly increased 7-21 days after the vaccination with pneumococcal polysaccharides (PPS). In contrast, non-T cells expressed increased responsiveness to rIL-2 only on post-vaccination day 7. Analysis of the proliferative response to rIL-2 among lymphocyte subsets (CD4+Leu8+, CD4+Leu8-, CD8+Leu8+, CD8+Leu8-, CD20+) in cultures of unseparated PBMC revealed that the CD8+Leu8- T cells expressed increased responsiveness 7-14 days after vaccination, whereas neither CD4+ (Leu8+ and Leu8-) nor CD8+Leu8+ T cells showed significantly increased responsiveness after vaccination. The CD20+ B cells, like non-T cells, expressed increased responsiveness to rIL-27 days after the vaccination only. Expression of the 55 kD low-affinity interleukin 2 receptor (IL-2R, CD 25) on freshly isolated PBMC, as judged by direct fluorescence staining with a MoAb anti-55 kD chain, was low (less than 3%) and an increased expression of this receptor was not detected following vaccination. In contrast, binding of 125I-labelled IL-2 to freshly isolated PBMC increased following vaccination (day 7). Scatchard plot analysis revealed a modest increase in the expression of high-affinity IL-2R (Kd = 1-2 pM)...

Regulation of interleukin 2 and interleukin 2 receptor gene expression in human T cells: I. Effect of Ca2+-ionophore on phorbol myristate acetate co-stimulated cells.

Chopra, R K; Nagel, J E; Chrest, F J; Boto, W M; Pyle, R S; Dorsey, B; McCoy, M; Holbrook, N; Adler, W H
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /08/1987 Português
Relevância na Pesquisa
65.85%
Human peripheral blood T lymphocytes were treated with phorbol myristate acetate (PMA), an activator of protein kinase C (PKC) activity, and with the calcium ionophore A23187. The resulting accumulation of specific mRNA for interleukin 2 (IL-2) and interleukin 2 receptor (IL-2R), as well as IL-2 secretion and membrane IL-2R expression were examined. At low concentrations (0.1 microM), A23187 synergized maximally with PMA to induce proliferation, to increase IL-2R mRNA levels and the expression of membrane IL-2R, and to produce a low but sufficient accumulation of IL-2 mRNA and IL-2 secretion. A high concentration of A23187 (1.0 microM) did not show any synergism for the accumulation of IL-2R mRNA, membrane IL-2R expression and inhibited the proliferation of PMA co-stimulated T cells. It did, however, induce maximum accumulation of IL-2 mRNA and IL-2 secretion.

Soluble interleukin 2 receptor in atopic eczema.

Colver, G. B.; Symons, J. A.; Duff, G. W.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 27/05/1989 Português
Relevância na Pesquisa
65.93%
OBJECTIVE--To determine whether serum soluble interleukin 2 receptor concentrations are related to disease activity in atopic eczema. DESIGN--Single cohort longitudinal study with controls. SETTING--Outpatient and general medicine departments in secondary referral centre. PATIENTS--Of 15 patients aged 17-57 with severe atopic eczema, all with acute exacerbations of disease, 13 were admitted to hospital and two treated as outpatients until the skin lesions had resolved or greatly improved. Nineteen controls gave single blood samples. INTERVENTIONS--Daily skin dressing with betamethasone valerate (0.025%) and ichthammol paste and tubular dressings. END POINT--Resolution of or considerable improvement in skin lesions. MEASUREMENTS AND MAIN RESULTS--Enzyme linked immunosorbent assays (ELISA) were used to measure serum soluble interleukin 2 receptor concentrations in blood samples taken on admission, at intervals subsequently, and on discharge. Clinical scores of disease activity were also made. Median concentrations on admission were significantly higher (770 U/ml) in the patients than the controls (300 U/ml). Concentrations fell significantly during treatment. In 25 assessments made at different times in 13 patients serum soluble interleukin 2 receptor concentration correlated significantly (R = 0.73) with clinical disease activity. CONCLUSIONS--Cellular immunopathogenic mechanisms contribute to atopic eczema. Immune activation can be measured in atopic eczema by measurements of soluble interleukin 2 receptor...

Transmembrane signaling of interleukin 2 receptor. Conformation and function of human interleukin 2 receptor (p55)/insulin receptor chimeric molecules

Fonte: The Rockefeller University Press Publicador: The Rockefeller University Press
Tipo: Artigo de Revista Científica
Publicado em 01/08/1987 Português
Relevância na Pesquisa
65.9%
Chimeric genes were constructed which gave rise to the expression of novel receptor molecules consisting of the extracellular domain of the human interleukin 2 receptor (IL-2-R; p55 or Tac antigen) joined to the transmembrane domain and either full-length or truncated cytoplasmic domain of the human insulin receptor (Ins-R). Expression studies using mouse T cell line EL-4 revealed that the chimeric receptors are able to manifest properties indistinguishable from the authentic IL-2-R. On the other hand, stimulation of the tyrosine kinase activity by IL-2 was not observed in the chimeric receptor with the entire cytoplasmic domain of the Ins-R. These findings thus shed light on the structural conformation and functioning of the IL-2-R complex.

Reduced expression of the interleukin-2-receptor gamma chain on cord blood lymphocytes: relationship to functional immaturity of the neonatal immune response

Zola, H.; Fusco, M.; Weedon, H.; Macardle, P.; Ridings, J.; Roberton, D.
Fonte: BLACKWELL SCIENCE LTD Publicador: BLACKWELL SCIENCE LTD
Tipo: Artigo de Revista Científica
Publicado em //1996 Português
Relevância na Pesquisa
75.92%
Mutation of the interleukin-2 (IL-2) receptor gamma chain, which also serves as a component of the receptor complexes for IL-4, 7, 9 and 15, results in severe immune deficiency. We hypothesized that the immunological immaturity of healthy neonates might be associated with low levels of expression of this receptor molecule. Using monoclonal antibody and a highly sensitive immunofluorescence method, we showed that IL-2 receptor gamma chain is expressed at significantly lower levels on cord blood cells compared with adult cells. IL-2-dependent T-cell activation in vitro was reduced in cord blood cells compared with adult cells, but B-cell responses to IL-4 were not obviously impaired. The lower level of expression of the gamma chain and some other cytokine receptor chains may contribute to the immunological immaturity of the newborn, by selectively depressing particular immunological mechanisms.

Interleukin-2 receptor antibody reduces rejection rates and graft loss in live-donor kidney transplant recipients

Lim, W.; Chang, S.; Chadban, S.; Campbell, S.; Dent, H.; Russ, G.; McDonald, S.
Fonte: Lippincott Williams & Wilkins Publicador: Lippincott Williams & Wilkins
Tipo: Artigo de Revista Científica
Publicado em //2009 Português
Relevância na Pesquisa
85.77%
Background. The use of interleukin-2 receptor antibody (IL-2Ra) induction has been associated with reduced rejection rates in both live and deceased donor kidney transplantation. However, the longer term effect of IL-2Ra induction on estimated glomerular filtration rates and graft and patient survival remains unclear. Methods. Using Australia and New Zealand Dialysis and Transplant Registry, live donor renal transplant recipients in Australia between 2001 and 2005 were studied (n=1106). Multiple organ graft recipients and those receiving T-cell depletive induction therapy or steroid- or calcineurin-free inhibitor regimens were excluded. Outcomes analyzed included the presence of rejection at 6 months, estimated glomerular filtration rate at 1 and 3 years, 5 years graft and patient survival. Results. A total of 41.7% of live donor renal transplant recipients received IL-2Ra induction. Recipients of IL-2Ra experienced a 51% reduction in the incidence of acute rejection (odds ratio 0.49, 95%CI 0.36-0.67; P<0.001). In addition, the use of IL-2Ra was associated with reduced overall graft loss (hazard ratio 0.58, 95%CI 0.35-0.96; P=0.03) and higher mean estimated glomerular filtration rate at 1 year but not 3 years. There was no association between IL-2Ra induction and death-censored graft loss or death with functioning graft. Conclusion. This registry analysis demonstrates that IL-2Ra induction in live donor kidney transplantation is associated with substantial clinical benefits of reduced risk of acute rejection...

Interleukin-2 receptor antibody does not reduce rejection risk in low immunological risk or tacrolimus-treated intermediate immunological risk renal transplant recipients

Lim, W.; Chadban, S.; Campbell, S.; Dent, H.; Russ, G.; McDonald, S.
Fonte: Blackwell Publishing Asia Publicador: Blackwell Publishing Asia
Tipo: Artigo de Revista Científica
Publicado em //2010 Português
Relevância na Pesquisa
85.78%
Aim: The use of interleukin-2 receptor antibody (IL-2Ra) induction has been associated with reduced rejection rates in renal transplant recipients. However, the effect of IL-2Ra induction on graft and patient outcomes in renal transplant recipients with differing immunological risk remains unclear. Methods: Using Australia and New Zealand Dialysis and Transplant Registry, renal transplant recipients in Australia between 1995 and 2005 were included. Recipients were stratified into low immunological risk (primary grafts with ≤2 human leucocyte antigen (HLA)-mismatches and panel-reactive antibody (PRA) < 10%) or intermediate immunological risk (subsequent grafts or >2 HLA-mismatches or PRA > 25%) recipients. Recipients receiving T-cell depletive induction therapy or steroid and/or calcineurin-free inhibitor regimens were excluded. Outcomes analysed included the presence of rejection at 6 months, estimated glomerular filtration rate at 1 and 5 years, graft and patient survival. Results: 218 of 1220 (18%) low-risk and 883 of 3204 (28%) intermediate-risk recipients received IL-2Ra. In intermediate-risk recipients, IL-2Ra induction was associated with a 26% reduction in the incidence of acute rejection; but this benefit was restricted only to recipients initiated on cyclosporine-based immunosuppressive regimens. In contrast...

Interleukin-2 and its receptor complex (alpha, beta and gamma chains) in in situ and infiltrative human breast cancer: an immunohistochemical comparative study

García-Tuñón Llanio, Ignacio; Ricote Belinchón, Mónica; Ruiz, Antonio; Fraile Láiz, Benito; Paniagua Gómez Alvarez, Ricardo; Royuela García, María del Mar
Fonte: BioMed Central Publicador: BioMed Central
Tipo: Artigo de Revista Científica Formato: application/pdf
Português
Relevância na Pesquisa
75.95%
The presence and distribution of interleukin-2 (IL-2) and its receptor complex (Ralpha, Rbeta, Rgamma) were studied in 52 women who were clinically and histopathologically diagnosed with breast tumours ( 17 in situ and 35 infiltrating), and in 13 women with benign fibrocystic lesions in the breast. Methods. Immunohistochemistry with antibodies against IL-2, IL-2Ralpha, IL-2Rbeta and IL-2Rgamma was used. A comparative semiquantitative immunohistochemical study between the three breast groups ( fibrocystic lesions, in situ tumours and infiltrating tumours) was performed. Results. IL-2 and its three receptor chains were immunodetected in the cytoplasm of epithelial cells. The three receptor chains were also detected on the cell surface. In fibrocystic lesions, immunoreactions to IL-2 (38.5% of cases), IL-2Ralpha (53.8%) and IL-2Rbeta (30.8%) were very weak, whereas immunoreaction to IL-2Rgamma (46.1%) was somewhat more intense. In in situ tumours, the percentages of cases that immunostained positively for IL-2 and its three receptor chains were similar to those observed in fibrocystic lesions, but immunostainings of the four antibodies were more intense. In infiltrative tumours, the percentages of positively stained cases and also immunostaining intensities were approximately twice that found for in situ tumours. Within infiltrating tumours...

Interleukin 2 receptor expression by macrophages in inflammatory bowel disease.

Mahida, Y R; Patel, S; Wu, K; Jewell, D P
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /12/1988 Português
Relevância na Pesquisa
65.88%
The expression of interleukin 2 receptor by macrophages from normal and inflamed terminal ileum and colon has been studied by using two monoclonal antibodies. In tissue sections from normal ileum and colon, scattered positive lymphocytes and only occasional weakly positive macrophages were seen. In ileal and colonic Crohn's disease or ulcerative colitis many positive macrophages and lymphocytes were seen in the lamina propria. These findings were confirmed by staining cytospin preparations of isolated intestinal mononuclear cells. The isolated macrophages were able to phagocytose opsonized zymosan and the majority were able to undergo a respiratory burst when triggered with opsonized zymosan or phorbol myristate acetate (PMA), suggesting that they were activated. Stimulation with interferon-gamma or lipopolysaccharide did not increase the number of macrophages staining with the antibodies to the interleukin 2 receptor. Therefore we postulate that a large majority of the macrophages expressing interleukin 2 receptor in inflammatory bowel disease are a recently recruited population of cells.

Increased in vitro release of soluble interleukin 2 receptor by colonic lamina propria mononuclear cells in inflammatory bowel disease.

Schreiber, S; Raedler, A; Conn, A R; Rombeau, J L; MacDermott, R P
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em /02/1992 Português
Relevância na Pesquisa
66.02%
Increased concentrations of the soluble form of the interleukin 2 receptor have been observed in the sera of Crohn's disease and ulcerative colitis patients. In this study we have observed the spontaneous release of soluble interleukin 2 receptor by unstimulated, isolated normal and inflammatory bowel disease colonic lamina propria mononuclear cells. Lamina propria mononuclear cells from Crohn's disease patients (median = 204 U/ml (interquartile range 126-396, n 17) secreted significantly (p less than 0.01) more soluble interleukin 2 receptor than normal controls (median = 124.5 U/ml (108-131), n 12). No statistically significant differences were seen between ulcerative colitis (median = 135 U/ml (92-196), n 20) and normal controls. Moreover, significantly (p less than 0.01) increased amounts of soluble interleukin 2 receptor were secreted by colonic diverticulitis lamina propria mononuclear cells (median = 259 U/ml (149-282), n 15) which were used as disease specificity controls. Time course experiments showed that the majority of soluble interleukin 2 receptor was released by isolated lamina propria mononuclear cells in the first six days of culture. Upon stimulation with pokeweed mitogen, Crohn's disease (median = 2258 U/ml (1435-3584)...

Interleukin-1? Activity in Necrotic Endothelial Cells is Controlled by Caspase-1 Cleavage of Interleukin-1 Receptor-2; Implications for Allograft Rejection

Gardner, Sarah E.; Humphry, Melanie; Bennett, Martin R.; Clarke, Murray C. H.
Fonte: ASBMB Publicador: ASBMB
Tipo: Article; published version
Português
Relevância na Pesquisa
65.87%
This is the final version of the article. It first appeared from ASBMB via http://dx.doi.org/10.1074/jbc.M115.667915; Inflammation is a key instigator of the immune responses that drive atherosclerosis and allograft rejection. IL-1?, a powerful cytokine that activates both innate and adaptive immunity, induces vessel inflammation after release from necrotic vascular smooth muscle cells (3 VSMCs). Similarly, IL-1? released from endothelial cells (ECs) damaged during transplant drives allograft rejection. However, IL-1? requires cleavage for full cytokine activity, and what controls cleavage in necrotic ECs is currently unknown. We find that ECs have very low levels of IL-1? activity upon necrosis. However, TNF? or IL-1 induce significant levels of active IL-1? in EC necrotic lysates without alteration in protein level. Increased activity requires cleavage of IL-1? by calpain to the more active mature form. Immunofluorescence and proximity ligation assays show that IL-1? associates with interleukin-1 receptor-2 (IL-1R2), and this association is decreased by TNF? or IL-1 and requires caspase activity. Thus, TNF? or IL-1 treatment of ECs leads to caspase proteolytic activity that cleaves IL-1R2, allowing IL-1? dissociation and subsequent processing by calpain. Importantly...

Interleukin-2 Receptor Serum Concentrations in Normal Pregnancy and Preeclampsia

Romero-Adrián,Tania; Ruiz,Ana; Molina-Vílchez,Rafael; Estévez,Jesús; Atencio,Ricardo
Fonte: Universidad del Zulia Publicador: Universidad del Zulia
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/04/2002 Português
Relevância na Pesquisa
85.95%
The purpose of this research was to assess interleukin-2 receptor serum levels in normal pregnancy and pre-eclampsia. Sera from 90 healthy pregnant women (30 for each trimester), 30 with pre-eclampsia and a group of 30 healthy non-pregnant were analyzed. Soluble interleukin-2 receptor was measured by specific double antibody enzymatic immunoassay (ELISA). Results were: 267.5 ± 12.3 (mean ± s.e.m) pg/mL in the uncomplicated first trimestre sample, 300.9 ± 14.5 pg/mL in the second trimester and 248.8 ± 12.5 pg/mL in the third. The non-pregnant control group had 443.7 ± 39.6 pg/mL, significantly different from normal pregnancy in all trimesters (p < 0.001). The concentration in pre-eclamptic patients was 382.2 ± 24.2 pg/mL, with p < 0.01 with regard to the normal third trimester group. The conclusion is that interleukin-2 receptor serum levels diminish in normal pregnancy and rise in preeclampsia. The first finding seems to be a protective mechanism to the fetal allograft. The latter, point to increased cellular activity.