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)

Cytokines production by OK-432-stimulated peripheral blood mononuclear cells (PBMC) were measured to investigate the in vitro function of macrophages (M phi) and lymphocytes. PBMC (1 x 10(6) cells/ml) were cultured with OK-432 (0.05 KE/ml) for 72 hr at 37 degrees C under 5% CO2, then interleukin 1 beta (IL-1 beta), interleukin 2 (IL-2) and soluble IL-2 receptor (sIL-2R) levels in the culture supernatants were measured by ELISA. While there was no significant differences of IL-1 beta production between patients with chronic active hepatitis type B (CAH-B) and controls, sIL-2R production (335 +/- 219 U/ml, mean +/- SD) was significantly decreased (p < 0.001) in patients with CAH-B. On the other hand, in pregnant women, production of both IL-1 beta (6.3 +/- 3.9 ng/ml, p < 0.01) and sIL-2R (300 +/- 169 U/ml, p < 0.001) were significantly lower than those in controls (13.5 +/- 3.8 ng/ml, 969 +/- 154 U/ml). These results suggest that the expression of IL-2R alpha on lymphocytes membrane is suppressed in patients with CAH-B, and that decreased M phi function is present in pregnant women.
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PMID:[OK-432-induced cytokines production by peripheral blood mononuclear cells]. 130 13

The response of the human CD4+ T-cell line Jurkat to infection with vaccinia virus was investigated. Virus titers peaked approximately 3 to 4 days after infection, while cell growth paralleled that of uninfected cells, indicating that growth rates were not appreciably affected by viral infection. Results from plaque assays and fluorescence-activated cell sorter (FACS) analyses of virus antigens demonstrated that a persistent infection in which the percentage of infected cells and the virus titers fluctuated from passage to passage was established. Further characterization of the persistent infection revealed that the virus influences cellular functions. Induction of interleukin-2 (IL-2) and IL-2 receptor alpha (IL-2R alpha) in Jvac cells was shown by enzyme-linked immunosorbent assay and FACS analysis, respectively. Hybridization of cellular RNA with cloned probes confirmed the increased IL-2 expression and demonstrated that Jvac cells also expressed more IL-6 but not gamma interferon (IFN-gamma) or IL-1 beta. Dual-antibody staining and FACS analysis for vaccinia virus antigens and IL-2R alpha indicated that IL-2R alpha expression was restricted to the infected cells. Jvac cells were also resistant to superinfection, an additional proof that persistent infection elicited phenotypic changes in the cell population.
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PMID:Stimulation of lymphokines in Jurkat cells persistently infected with vaccinia virus. 134 94

The immunomodulatory effect of Mycobacterium tuberculosis-derived lipoarabinomannan (LAM) on mitogen/antigen-induced expression of mRNAs for a number of cytokines in human monocytic cell line Mono-Mac-6 and in T cell line Jurkat was investigated. Interestingly, LAM exhibited a down-regulatory effect on the accumulation of mRNAs for IL-2, IL-3, granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-2 receptor alpha (IL-2R alpha) in T cells co-stimulated with phytohaemagglutinin-P (PHA) and 4 beta-phorbol-12-myristyl-13-acetate (PMA). In human Mono-Mac-6 cells. LAM has a weak inhibitory effect on the lipopolysaccharide (LPS)-induced mRNA accumulation for IL-1 beta, a slight stimulatory effect on mRNAs accumulation for IL-8 and tumour necrosis factor-alpha (TNF-alpha), but clearly no effect on mRNA accumulation for intercellular adhesion molecule-1 (ICAM-1). These findings imply that LAM may contribute to the immunologic defects associated with a number of mycobacterial infections by modulating these mediators.
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PMID:Specific inhibition of mRNA accumulation for lymphokines in human T cell line Jurkat by mycobacterial lipoarabinomannan antigen. 137 54

Standard dialysis with cuprophane membranes is known to stimulate the immune system. As a result of activation of macrophages various interleukins and tumor necrosis factor (TNF) are secreted, presenting further evidence of the poor biocompatibility of cuprophane. We investigated the immunogenic properties of three modern high-flux membranes. Seven patients were studied during hemodiafiltration sessions using either a polysulfone (F60, Fresenius), a polymethylmetacrylate (BK 2.1, Toray) or a cellulose triacetate (FB-210 U, Nipro) dialyzer in a hemodiafiltration procedure. Serial measurements were made during each treatment of interleukin-1 beta (II-1 beta), TNF, soluble IL-2 receptor (sII-2r), soluble CD4 (sCD4), soluble CD8 (sCD8), interferon gamma (IFNg) and neopterin. In contrast to the known increase of IL-1 beta, IL-2r and TNF with cuprophane membranes, none of the modern high-flux dialyzers stimulated the production of these factors. Significant decreases of neopterin and sCD4 were observed. IFNg and sCD8 did not change significantly. Our results suggest that the modern high-flux dialyzers are non-immunogenic, and thus provide further evidence of the superior biocompatibility of synthetic or semisynthetic membranes over the conventional cuprophane.
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PMID:Biocompatibility of high-flux membranes. 139 92

We have evaluated the synergistic effects of interleukin-1 (IL-1) and interleukin-2 (IL-2) on the induction of lymphokine-activated killer (LAK) activity. Subcutaneous injection of recombinant IL-1 beta at an initial dose of 1 x 10(4) U was given to nine patients (five with renal cell carcinoma, two with bladder carcinoma, one with renal pelvic tumor, one with testicular tumor) on days 1 and 2 weekly for 4 weeks. The dose was increased weekly up to 4 x 10(4) U, if it was well tolerated. Peripheral blood mononuclear cells (PBMC) were isolated from patients on day 3 in the 2nd and 4th weeks, and LAK activity of PBMC against Daudi cells was measured using a 4-h 51Cr-release assay at an effector:target cell ratio of 20:1, after incubation with 50 U/ml of recombinant IL-2 for 72 h. Proliferation of PBMC was measured by tritiated thymidine incorporation after incubation with IL-2 for 72 h. IL-2 receptor (IL-2R)-positive cells in PBMC were enumerated using monoclonal antibody and flow cytometry. Mean values of LAK activity induced by IL-2 were significantly augmented after administration of IL-1 beta (p less than 0.01). IL-1 beta, however, did not enhance proliferation of PBMC caused by IL-2, nor did it increase the number of IL-2R-positive cells in peripheral blood lymphocytes of the patients. Results suggest that combination of IL-1 and IL-2 has synergistic antitumor activity in treatment of malignant diseases.
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PMID:Enhancement of lymphokine-activated killer activity induction in vitro by interleukin-1 administered in patients with urological malignancies. 151 24

EL 4-6.1 cells, variants of the murine EL4 thymoma cell line, can be activated by interleukin 1 (IL-1) or phorbol 12-myristate-13-acetate (PMA), or PMA+IL-1 to secrete interleukin 2 (IL-2) and interleukin 4 (IL-4) and to express the IL-2 receptor (IL-2R). To compare the different activation pathways, we examined the effects of staurosporine (STAR) and 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H7), two protein kinase C (PKC) inhibitors, on the induction of interleukin secretion and IL-2R expression in these cells. We report here that nanomolar concentrations of STAR strongly potentiated (20- to 30-fold) the production of IL-2 or IL-4, when EL 4-6.1 cells were induced by IL-1 alpha (or IL-1 beta) alone. By contrast, at identical concentrations, STAR dose-dependently inhibited the production of IL-2 and IL-4 resulting from PMA or PMA+IL-1 cell treatment. STAR also negatively affected the expression of IL-2R, which was dependent on PMA-sensitive PKC with either IL-1, PMA, or PMA+IL-1 stimulation. The changes in interleukin production and IL-2R expression in EL 4-6.1 activated cells were correlated with changes at the mRNA level measured by quantitative polymerase chain reaction (PCR). This finding suggests a pretranslational effect of the drug. At micromolar concentrations, H7 showed the same effects as STAR, but only increased IL-1-triggered interleukin secretions twofold. We observed that the action of PKC inhibitors did not result from modification of IL-1 receptor (IL-1R) expression in EL 4-6.1 cells. Thus, our data show that PKC inhibitors clearly distinguish between IL-1 and PMA stimulatory pathways. In addition, they suggest that the IL-1 stimulatory pathway involves PKC(s) [or other undefined kinase(s)] which regulate this pathway and differ from PKC(s) activated by PMA.
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PMID:Contrasting effects of the protein kinase C inhibitor staurosporine on the interleukin-1 and phorbol ester activation pathways in the EL4-6.1 thymoma cell line. 156 50

Crohn's disease (CD) and ulcerative colitis (UC) show an intestinal activation of T cells and macrophages within the inflamed lesions. The aim of the present prospective study was to determine whether circulating interleukins (IL) represent useful markers of immune activation in vivo and to characterize their respective roles in monitoring disease activity. Serum concentrations of the soluble IL-2 receptor (sIL-2R), IL-6 and IL-1 beta were measured in 10 patients with CD and 10 patients with UC before, at day 10 and 2 years after resection of inflamed bowel segments. The data were correlated with neopterin, C-reactive protein and other standard parameters of disease activity. Preoperatively, mean sIL-2R concentration was 495 +/- 62 U/ml (mean +/- SEM; healthy controls; 210 +/- 25 U/ml; p less than 0.02) in CD and 705 +/- 120 U/ml (p less than 0.00002) in UC. The corresponding IL-6 serum concentrations were 37 +/- 6 U/ml in CD (controls: 11 +/- 0.6 U/ml; p less than 0.0036) and 33 +/- 6 U/ml (p less than 0.04) in UC. Two years postoperatively, sIL-2R was still elevated in 6 out of 9 patients in both disease groups. These patients did not differ from the remaining group with respect to disease activity. Serum IL-6, elevated in 7 patients with CD and in 6 patients with UC at day 10 postoperatively, had returned to normal in all patients by this time.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Soluble interleukin-2 receptor, interleukin-6 and interleukin-1 beta in patients with Crohn's disease and ulcerative colitis: preoperative levels and postoperative changes of serum concentrations. 163 22

Serum cytokine profiles were evaluated in immunized and nonimmunized human volunteers after challenge with infectious Plasmodium falciparum sporozoites. Three volunteers had been immunized with x-irradiated sporozoites and were fully protected from infection. Four nonimmune volunteers all developed symptomatic infection at which time they were treated. Sera from all volunteers were collected at approximately 20 time points during the 28-d challenge period; levels of IL-1 alpha, IL-1 beta, IL-2, IFN-gamma, tumor necrosis factor-alpha, IL-4, IL-6, granulocyte macrophage-colony-stimulating factor, and soluble CD4, CD8, and IL-2 receptor (sCD4, sCD8, and sIL-2R, respectively) were determined by ELISA. C-reactive protein (CRP) was assayed by radial immunodiffusion. Parasitemic subjects developed increases in CRP and IFN-gamma, with less marked increases in sIL-2R and sCD8; the other cytokines tested did not change. CRP increases were abrupt and occurred at the onset of fever (day 14 after challenge). IFN-gamma increases were also abrupt, preceding those of fever and CRP by one day. Increases in sIL-2R and sCD8 were more gradual. Increases in fever, CRP, IFN-gamma, and sCD8 were concordant in each volunteer. Early IL-6 increases were noted in the protected vaccinees. Thus, after challenge with virulent P. falciparum, unique systemic cytokine profiles were detectable both in immunized, nonparasitemic volunteers and in unvaccinated, parasitemic subjects. The contrasting cytokine profiles in the two groups may relate to mechanisms of protection and immunopathology in experimental human malaria.
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PMID:Serum cytokine profiles in experimental human malaria. Relationship to protection and disease course after challenge. 164 22

Human cytomegalovirus (HCMV) immediate early (IE) genes act as trans-acting factors to upregulate various viral promoters. We used various IE plasmid constructs in transient transfection assays and demonstrated that the HCMV IE2 gene product upregulated expression from the interleukin (IL)-2 and IL-2 receptor (IL-2R) promoters and increased amounts of endogenous, steady-state IL-2 and IL-2R RNA. In marked contrast, the IE1 gene product, which can upregulate the major IE promoter and the IL-1 beta promoter, had no effect on the IL-2 and IL-2R promoters. These studies suggest a role for the HCMV IE2 gene product as a modulator of the inflammatory response associated with HCMV infection.
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PMID:The immediate early genes of human cytomegalovirus upregulate expression of the interleukin-2 and interleukin-2 receptor genes. 165 52

Several immune mechanisms are likely to be responsible for renal allograft rejection. The relative importance of delayed-type hypersensitivity versus cytotoxic T lymphocytes is controversial. We analyzed human renal allografts biopsies for intragraft expression of IL-1 beta, IL-6, and TNF alpha genes--putative mediators of DTH--as well as IL-2, IL-2 receptor (R) beta, and a CTL-specific serine protease gene. Total RNA was extracted from tissue samples and the mRNA fraction was converted to cDNA using oligo dT and reverse transcriptase. Then cDNA was amplified by the polymerase chain reaction (PCR) for 35 cycles using specific oligonucleotide primers. Each PCR analysis included beta-actin oligonucleotide primers to coamplify this constitutively expressed gene as an internal control. A total of 24 core allograft biopsies were studied and classified into a 3 histological categories: acute cellular rejection, equivocal components of rejection, and no evidence of rejection. There was no statistically significant difference in beta-actin expression among these histologic categories (P greater than 0.08). Interestingly, in this sample size, no significant difference was found between rejecting and nonrejecting samples for transcripts of any of the cytokines or IL-2R beta mRNAs. Apparently, DTH-like mechanisms are present in all allografts. However, detection of CTL-specific serine protease gene expression was almost exclusive to rejecting samples (P less than 0.003). These findings suggest that activation of CTLs play an active, but hardly exclusive, role as effectors of graft dysfunction in the rejection process. While this study does not define the relative importance of the genes examined, it does suggest that evidence of CTL-specific serine protease expression may provide a means of monitoring for rejection episodes or as a diagnostic aid when conventional diagnostic criteria are not conclusive.
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PMID:The strong correlation of cytotoxic T lymphocyte-specific serine protease gene transcripts with renal allograft rejection. 173 89


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