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)

Immune activation is central to many immune disorders. Clinical investigations have shown that immune activation can be quantified by measurements of soluble immune activation products in serum. Most in vitro studies of these immune activation products have focused on single products. In this study the specific cell sources and the major lymphokines inducing multiple activation products were investigated. In vitro addition of interferon-gamma (IFN-gamma) or IL-2 stimulated peripheral blood mononuclear cells to produce neopterin, beta 2-microglobulin (beta 2-M) and soluble IL-2 receptor (sIL-2R). These two lymphokines can act independently, because neutralizing antibodies to one of the lymphokines did not block the inducing activity of the other. Tumour necrosis factor-alpha (TNF-alpha) was also investigated and shown to be a less powerful inducer than IL-2 or INF-gamma. Separated lymphoid subpopulations responded differently to specific lymphokines. Monocytes produced only neopterin and only in response to INF-gamma. T cells released beta 2-M and sIL-2R in response to IL-2. B cells, however, were capable of producing all three immune activation products. Neopterin production in B cells was induced by either INF-gamma of IL-2, indicating that B cells have additional mechanisms for responding to lymphokines. To investigate whether these in vitro findings also occur in vivo, sera from patients who had received either rIL-2 or INF-gamma treatment were tested. INF-gamma administration led to substantial increases in serum neopterin but only a moderate beta 2-M increase and no increase in the serum sIL-2R levels. rIL-2 administration caused a substantial increase of all three serum immune activation products, consistent with our in vitro findings. The results confirm that increased serum levels of soluble immune activation products are indicators of increased cytokine production by lymphocytes and monocytes and also that B cells can be a prominent source of immune activation products.
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PMID:Different lymphoid cell populations produce varied levels of neopterin, beta 2-microglobulin and soluble IL-2 receptor when stimulated with IL-2, interferon-gamma or tumour necrosis factor-alpha. 160 39

A monocytic cell line, THP-1, was acutely infected with HIV, and the effects of various factors including INF-gamma, LPS, IL-2, and IL-6 were analyzed. While IFN-gamma suppressed HIV production, IL-2 and IL-6 augmented it. The suppressive effect of IFN-gamma was not overcome by IL-2 or by LPS. We studied whether the induction of IL-2 receptor alpha (IL-2R alpha) expression by those factors was related to HIV infection or not. By immunofluorescence analysis using monoclonal anti-IL-2R alpha antibody, we observed that HIV infection itself induced IL-2R alpha expression moderately in U937 and THP-1, and IL-6 as well as IFN-gamma highly induced IL-2R alpha expression both in uninfected and infected THP-1. Although induction of HIV production and IL-2R alpha expression by cytokines seem not to be directly correlated, these results suggest that soluble IL-2R alpha increased in AIDS patients might be at least partly derived from infected monocyte/macrophages activated by various cytokines, especially IL-6, which is mainly produced by themselves.
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PMID:Effect of cytokines on HIV release and IL-2 receptor alpha expression in monocytic cell lines. 169 Dec 89

Psoriasis represents inflammatory skin disorders characterized by significant changes in cellular immunity, particularly exhibiting alterations in T lymphocyte-related functions. Early psoriatic lesions have been reported to show an infiltration of activated helper T cells. Elevated levels of interleukin 2 (IL-2), IL-2 receptor (IL-2R), and interferon-gamma (INF-gamma) are associated with an early activation of T cells. To examine local activation of T cells in psoriatic skin, the amounts of activated T cell products, IL-2, secretory form of IL-2R (sIL-2R) and INF-gamma were measured in the fluids of suction blisters raised on psoriatic skin. sIL-2R levels were significantly elevated in the suction blister fluids raised on psoriatic involved skin compared with those on normal and psoriatic uninvolved skin. On the other hand, neither IL-2 or IFN-gamma was detected in the suction blister fluids either from normal, psoriatic uninvolved, or involved skin. However, we could detect IFN-gamma and IL-2 in the psoriatic scale extracts. Although we failed to detect IL-2 and IFN-gamma in the suction blister fluids, the increased levels of sIL-2R in the suction blister fluids from the psoriatic lesional skin indicate local activation of T cells in psoriatic lesional skin.
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PMID:Interleukin 2, soluble interleukin 2 receptor, and interferon-gamma in the suction blister fluids from psoriatic skin. 206 14

To assess the role of decidual cells (DC) in the maintenance of pregnancy, immunosuppressive activity of culture supernatants from human DC were investigated. Dispersed DC suspensions from decidual tissue of early pregnancies were prepared by an enzyme digestion method using collagenase and DNase, and were enriched over 90 per cent without contamination of macrophages and lymphocytes in the fraction, with specific gravity between 1.033 and 1.044 (fraction 2 [Fr2] ) by a Percoll discontinuous density gradient method. The culture supernatants of Fr2 cells suppressed the responses of normal peripheral blood lymphocytes to PHA, MLR, and killer T cell generation at the 50 per cent concentration. To determine the mechanism of the immunosuppressive activity of the culture supernatants, the effect of the supernatants on interleukin-2 and gamma-interferon production, as well as IL-2 receptor expression, on PBL was investigated. The supernatants from 3 x 10(6)/ml of DC cells inhibited not only IL-2 and gamma-INF production, but also IL-2 receptor expression, compared with normal controls. The supernatants also suppressed immunoglobulin (IgG and IgM) production by pokeweed mitogen-stimulated B cells. To purify the suppressor factor from culture supernatants of DC, serum free culture supernatants of 3 x 10(6)/ml of DC, which showed 32 per cent of inhibitory activity on MLR, were applied to gel filtration. Fractions between mw 67,000 and 43,000 suppressed the MLR. These results suggest that DC from decidua of early pregnancy excrete an immunosuppressive factor with a molecular weight between 43,000 and 67,000 daltons.
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PMID:Characterization and analysis of soluble suppressor factor from early human decidual cells. 252 5

An immunosuppressive factor was obtained from culture supernatants of early human decidual cells. The suppressor factor was concentrated by gel filtration in a fraction with a molecular weight between 43,000 and 67,000 daltons. It was further purified by biochemical methods. Four peaks were obtained in the fraction with molecular weight between 43,000 and 67,000 daltons by anion exchange chromatography. Only the second peak had immunosuppressive activity in MLR. Lentil-lectin affinity chromatography of this suppressor factor showed that the suppressor factor had no affinity for lentil-lectin sepharose. Isoelectric focusing of the suppressor factor demonstrated four bands. The protein isoelectric (PI) point was approximately 7.50 in one band and between 6.85 and 7.35 in the other three bands. These results demonstrate that the suppressor factor is not glycoprotein but protein, whose PI is between 6.85 and 7.50. The suppressive effect of this purified factor on lymphokine production and lymphocyte activation was investigated. The addition of the purified suppressor factor to a culture of PBL stimulated with PHA suppressed not only IL-2 production and gamma-INF production, but also BSF-2 production. IL-2 receptor expression and transferrin receptor expression of PBL stimulated with PHA were also suppressed by addition of the suppressor factor. These results demonstrate that this suppressor factor inhibits lymphokine production and lymphocyte activation.
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PMID:Immunochemical characterization of the suppressor factor from early human decidual cells. 279 18

The aim of the study was to investigate whether a regular moderate endurance exercise programme influenced the in vitro cytokine synthesis by stimulated whole blood cultures. To this end, eight healthy subjects exercised moderately by running for 3-5 h a week over a period of 12 weeks, whilst seven other healthy subjects served as the control group. The intensity of the exercise was determined by lactic acid concentrations in the blood which were maintained between 1.8 and 2.5 mmol x l(-1). Over the period of training the running velocity producing the 4 mmol x l(-1) lactic acid threshold increased from 2.86 (SD 0.83) m x s(-1) to 3.06+/-0.79 m x s(-1) (P < or = 0.008). Blood samples were taken at rest before and after the training programme. The following blood parameters were determined: leucocyte count, differential leucocyte count, lymphocyte subpopulations [CD14 positive (+)/CD45+, CD4+/ CD25+, CD8+, CD16+/CD122+]. Whole blood cultures were stimulated with lipopolysaccarides [interleukin (IL)-1 beta and IL-6] and staphylococcal enterotoxin B [IL-2, soluble interleukin 2 receptor (sIL2-R) and interferon (IFN)-gamma]. Cytokine concentrations in the supernatants were measured using an enzyme-linked immunosorbent assay. The white blood cell count, differential leucocyte count, lymphocyte subset distribution and the expression of the CD25 and CD122 antigen on lymphocytes were unchanged by training. After the training programme the IL-1 beta production changed significantly [1496 (SD 264) pg ml(-1) before, compared to 2127 (SD 672) pg ml(-1) after training, P < or = 0.008]. In the control group these parameters remained unchanged. With respect to changes in the values in both groups the syntheses of IL-1 beta (P < or = 0.023) and IL-6 (P < or = 0.021) were significantly higher after regular training. The syntheses of IL-2, sIL-2 and INF-gamma were not significantly influenced. Regular endurance exercise influenced the in vitro production of monocyte derived cytokines, while the effect of exercise on the cytokines synthesized by T-cells appeared to be of lesser importance.
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PMID:Increased concentrations of interleukin 1-beta in whole blood cultures supernatants after 12 weeks of moderate endurance exercise. 1034 59

(n-3) PUFA influence immune function in adults and may also affect immune maturation during development. This randomized trial is, to our knowledge, the first to investigate whether fish oil supplementation in late infancy modifies immune responses. The study was a 2 x 2 intervention in 64 healthy Danish infants, who received cow's milk or infant formula alone or with fish oil (FO) (3.4 +/- 1.1 mL/d) from 9 to 12 mo of age. Before and after the intervention, fatty acid composition of erythrocyte membranes, plasma IgE, C-reactive protein, and soluble IL-2 receptor concentrations were measured. TNF-alpha, INF-gamma, and IL-10 concentrations in whole-blood cultures, stimulated for 22 h with LPS+phytohemaglutinin (PHA) or Lactobacillus paracasei, were also determined. IgA was measured in feces when infants were 10 mo of age. FO supplementation effectively raised erythrocyte (n-3) PUFA (P < 0.001), increased L. paracasei-induced INF-gamma (P = 0.05) and tended to reduce LPS+PHA-induced IL-10 (P = 0.08). The FO intervention did not affect any of the other analyzed immune variables. The erythrocyte content of eicosapentanoic acid was negatively associated with LPS+PHA-induced IL-10 (r = -0.38, P = 0.02). Feeding milk rather than formula did not affect cytokine production, but plasma soluble IL-2 receptor concentration was greater in the formula group than in the cow's milk group (P = 0.03). Since the capacity to produce INF-gamma has been proposed as a maturation marker for the immune system in early life, this study suggests a faster immune maturation with FO supplementation with no apparent reduction in immune activation. The implications for later health need further investigation.
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PMID:Fish oil supplementation modulates immune function in healthy infants. 1737 72

We previously identified an indole-3-propanamide derivative, 3-[1-(4-chlorobenzyl)indol-3-yl]-N-(pyridin-4-yl)propanamide (AD412), as a potential immunosuppressive agent. Here, we document that AD412 inhibited the proliferative response of CD3/CD28-stimulated human T cells without inhibiting their interleukin 2 (IL-2) production and also inhibited the proliferation of CTL-L2 cells in response to IL-2. These results prompted us to analyze the effect of our compound on the three main signaling pathways coupled to the IL-2 receptor. We provide evidence that AD412 inhibited the JAK1/3-dependent phosphorylations of Akt, STAT5a/b, and ERK1/2 in IL-2-stimulated CTL-L2 cells. In contrast, AD412 had little effect on the JAK1/2-dependent INF-gamma-induced phosphorylation of STAT1 in U266 cells. This suggested a preferential inhibition of JAK3 over JAK1 or JAK 2 activities by AD412 that was confirmed by in vitro kinase assays with purified JAK2 and JAK3 kinases. In addition, we provide evidence that the inhibition of IL-2 response by AD412 was not due to inhibition of IL-2Ralpha up-regulation because neither AD412 nor JAK3 inhibitors described previously [4-[(3-bromo-4-hydroxyphenyl)amino]-6,7-dimethoxyquinazoline (WHI-P154) and alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamid (AG-490)] significantly inhibited IL-2-induced IL-2Ralpha overexpression. Finally, we further document the immunosuppressive activity of AD412 in vivo by showing that its administration per os significantly prolonged heart allograft graft survival. This molecule may thus represent an interesting lead compound to develop new immunosuppressive agents in the field of transplantation and autoimmune diseases.
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PMID:A novel indole-3-propanamide exerts its immunosuppressive activity by inhibiting JAK3 in T cells. 1971 Mar 67