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)

We cloned the cDNA of turkey interleukin-2 (IL-2), initially using oligonucleotide primers based on the sequence of the chicken IL-2 gene. Compared with the only other cytokines available for comparison, the interferons (IFN), the coding regions of the turkey and chicken IL-2 genes are much less conserved (86.24% nucleotide identical and 69.93% amino acid identical). The lack of nucleotide conservation was spread across the entire length of the coding region. In comparison, the promoters of the two avian IL-2 genes shared a high degree of identity (95.71% identical over 380 nucleotides). Phylogenetic analysis shows that turkey and chicken IL-2 have diverged to a greater extent than IL-2 from closely related mammalian species. Surprisingly, considering the low level of amino acid identity, including residues known to be important in binding the IL-2 receptor in mammalian species, both turkey and chicken IL-2 cross-react in functional assays.
J Interferon Cytokine Res 2000 Feb
PMID:Turkey and chicken interleukin-2 cross-react in in vitro proliferation assays despite limited amino acid sequence identity. 1071 51

Curative surgery for gastrointestinal malignancy is commonly thwarted by local tumour recurrence. The heparin-binding growth factors, basic fibroblast growth factor (bFGF), heparin-binding epidermal growth factor-like growth factor (HB-EGF) and vascular epidermal growth factor (VEGF) are all implicated in the metastatic process, but whether or not these essential growth factors are produced by the activated peritoneum is unknown. This study reveals that peritoneal mesothelial cells constitutively express mRNA for bFGF, HB-EGF and two VEGF spliced variants, VEGF121 and VEGF165. Mesothelial activation with interleukin (IL)-1b or tumour necrosis factor (TNF)-a produced an up-regulation of mRNA for HB-EGF and VEGF, but not bFGF expression. IL-6 failed to stimulate growth factor expression, whereas IL-2 produced a marked suppression in HB-EGF and bFGF, but not VEGF expression. Mesothelial cells were shown to predominantly express mRNA for the intermediate affinity (bg(c)) IL-2 receptor. Cytokine-induced growth factor up-regulation was confirmed at the protein level using Western blotting of mesothelial cell lysates for HB-EGF and culture supernatant enzyme-linked immunosorbent assay for VEGF. The production of these growth factors by human mesothelial cells may play a significant role in post-operative peritoneal tumour recurrence. Their common heparin-binding property offers a potential therapeutic target for manipulating the growth factor environment of the human peritoneum.
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PMID:Activated mesothelial cells produce heparin-binding growth factors: implications for tumour metastases. 1073 11

Interleukin-4 (IL-4) regulates the expression of the 55-kDa alpha-subunit (CD25) of the IL-2 receptor complex in human B lymphocytes. This report suggests that the cAMP/protein kinase A (PKA) component of the IL-4 receptor signalling programme in human tonsillar B cells has a functionally important role in regulating expression of the CD25 gene by attenuating activity of a protein binding to a potent negative regulatory element (NRE) in the CD25 promoter; this effect can be mimicked by agents that elevate cAMP and blocked by inhibitors of PKA but not protein kinase C (PKC). In a B-cell line that fails to elevate cAMP, attenuate NRE-binding protein (NRE-BP) activity or express CD25 following IL-4 treatment, stimulation of cAMP accumulation by forskolin facilitates IL-4-mediated induction of both the endogenous gene and an exogenous reporter gene under the control of a minimal promoter/enhancer fragment of the CD25 gene.
Cytokine 2000 Jun
PMID:A functional role for interleukin (IL)-4-driven cyclic amp accumulation in human b lymphocytes. 1084 54

Interleukin-9 (IL-9) is a Th2-derived cytokine that uses the gamma-chain of the IL-2 receptor for signaling. Therefore, the responsiveness of human Th1 and Th2 cell clones to IL-9 was measured by examining the ability of this cytokine to prevent apoptosis induced by IL-2 deprivation. A time course study demonstrated that both subsets of T cell clones underwent apoptosis with similar kinetics when deprived of IL-2 and that viability could be maintained by the addition of either IL-4 or IL-7. Interestingly, IL-9 prevented apoptosis in only 2 (Th2) of 14 clones tested. Analysis of IL-9R alpha subunit expression on 18 T cell clones revealed that IL-9 responsiveness was directly proportional to the expression of the high-affinity receptor. IL-9 responsiveness was also dependent on long-term culturing because neither freshly isolated nor 3-day phytohemagglutinin (PHA)-stimulated peripheral blood lymphocytes (PBL) expressed IL-9R alpha. In summary, the data showed that IL-9 can rescue only a small subset of Th2 cells from apoptosis induced by growth factor withdrawal and that expression of IL-9R alpha is required for the antiapoptotic signals mediated by this cytokine.
J Interferon Cytokine Res 2000 Jun
PMID:Rescue of human T cells by interleukin-9 (IL-9) from IL-2 deprivation-induced apoptosis: correlation with alpha subunit expression of the IL-9 receptor. 1088 17

Most of the data accumulated to date on the immunoregulatory effects of prostaglandins (PG) on T cell activation stem from the archetypal inhibitory effect of PGE(2). In this study we provide instead, the first evidence that exogenous PGB(2), a catabolic metabolite of PGE(2), synergizes with signals delivered by T cell receptor (TCR) engagement to induce interleukin-2 (IL-2) production and IL-2 receptor (IL-2R) alpha-expression in Jurkat cells. Accordingly, PGB(2) enhances the proliferation of anti-CD3-activated peripheral blood lymphocytes (PBL). In terms of cellular signaling, we present evidence that PGB(2) activates tyrosine kinase activities and efficiently increases c-fos mRNA expression and nuclear factor-kappa B (NF-kappa B) translocation to the nucleus. Owing to these features, PGB(2) appears as a new lipid mediator capable of delivering an ancillary signal leading to T lymphocyte activation.
Eur Cytokine Netw 2000 Jun
PMID:Prostaglandin B(2) delivers a co-stimulatory signal leading to T cell activation. 1090 9

We report a case of Epstein-Barr virus (EBV)-associated lymphoproliferative disorder (LPD) which developed after chemotherapy for hemophagocytic lymphohistiocytosis (HLH), who had no history of immunodeficiency or familial X-linked LPD. In HLH, the presence of EBV in T-cells was confirmed by a combination of in situ hybridization (ISH) and immunostaining. Southern blot analysis using EBV-TR and immunoglobulin JH probes revealed oligoclonal proliferation of B-cells in each organ involved by abnormal B-lymphoid cells at autopsy. Combined ISH and immunostaining disclosed the presence of EBV in proliferating B-cells. Cytokine analysis during the period of T-cell activation in HLH revealed marked elevation of interferon (IFN) gamma, interleukin (IL)-10 and soluble IL-2 receptor (sIL-2R) and mild to moderate increases of tumor necrosis factor (TNF)-alpha were observed, while IFN gamma, IL-10 and sIL-2R were elevated initially during the HLH phase, which then decreased as LPD developed and B-cell proliferation predominated. Immunosuppressive chemotherapy for HLH may then have allowed latent EBV in B lymphocytes to induce transformation and oligoclonal proliferation of B-cells, finally resulting in LPD. Mechanisms of EBV-induced cell proliferation remain unclear, but alteration of various cytokines may be responsible for it.
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PMID:Epstein-Barr virus (EBV)-induced B-cell proliferative disorder after chemotherapy in a patient with hemophagocytic lymphohistiocytosis with associated EBV-induced T-cell proliferation. 1104 20

Previously, we demonstrated that in vitro treatment of B16F10 murine melanoma cells with interleukin-2 (IL-2) enhances proliferation and metastasis. To further investigate the role played by IL-2 in human melanomas, we studied the expression of IL-2/IL-2 receptor and the effect of IL-2 on the proliferation of melanoma cell lines derived from primary (A375 and RMS cell lines) and metastatic (Hs294T cell line) tumours. We found a constitutive expression of cytoplasmic IL-2 and alpha, beta and gamma-subunits of the IL-2R on the surface of the three melanoma cell lines. The presence of IL-2 in the culture increased the proliferation rate in A375 and RMS cell lines, but no effect was observed in Hs294T metastatic cells. Biologically active IL-2 could be found in the supernatant of the three melanoma cell lines, particularly in A375 and RMS cells, in which an inhibition of the proliferation rate was observed when IL-2 was blocked. Moreover, the combination of anti-IL-2R beta and anti-IL-2R gamma blocking antibodies induced a significant down-regulation of cell proliferation in the three melanoma cell lines, and the combination of anti-IL-2R alpha, anti-IL-2R beta and anti-IL-2R gamma blocking antibodies inhibited IL-2-mediated growth stimulation in A375 and Hs294T cell lines. In RMS cells, a more significant effect was observed when only IL-2R gamma was blocked. Finally, exogenous IL-2 modulated the IL-2 endogenously produced by melanoma cells. These data show that IL-2 may modulate the growth of melanoma cells through autocrine or/and paracrine mechanisms.
Eur Cytokine Netw 2000 Dec
PMID:Interleukin-2 enhances the growth of human melanoma cells derived form primary but not from metastatic tumours. 1112 10

Interleukin-2 (IL-2) plays an important role in adaptive immune responses. These responses differ between females and males and may be due to the sex steroid estrogen. In this investigation we show that estrogen suppresses IL-2 production from activated peripheral blood T cells and CD4+ T cell lines at the transcriptional level. Suppression of IL-2 occurred at short term, high 17-beta-estradiol concentrations as well as longer term lower 17-beta-estradiol concentrations. In CD4+ Jurkat T cells, suppression of IL-2 was associated with decreased nuclear binding of two important IL-2 promoter transcription factors: NFkappaB and AP-1. The decreased nuclear binding of NFkappaB occurred in the setting of estrogen-induced increases in IkappaBalpha protein levels, an important inhibitor of NFkappaB nuclear translocation. 17-beta-Estradiol was also shown to inhibit IL-2 receptor (IL-2R) expression in activated peripheral blood T cells. Estrogen-induced suppression of IL-2 and its receptor may have many ramifications for our understanding of immune and autoimmune sexual dichotomies, immune responses during pregnancy, and potential therapeutic intervention with hormone agonists and antagonists.
Cytokine 2001 Jun 21
PMID:17-beta-estradiol suppresses IL-2 and IL-2 receptor. 1149 93

Activated T cells from elderly humans are known to often display a decline in interleukin-2 (IL-2) production. However, the possible effects of aging on the expression of IL-2 receptor (IL-2R) subunits by human T cells are more controversial and less well characterized. In the present investigation, the surface expression of IL-2Ralpha, IL-2Rbeta, and IL-2Rgamma subunits on resting and activated T cells from 15 sets of elderly and young humans was evaluated. The results showed no significant differences in the average expression of IL-2Ralpha, IL2Rbeta, and IL-2Rgamma on resting T cells from elderly and young subjects, with values of 10% or less. Similarly, no significant differences were found in the mean levels of IL-2Ralpha, IL-2Rbeta, and IL-2Rgamma on T cells from elderly and young subjects stimulated with anti-Ig cross-linked anti-CD3 (monoclonal antibody [mAb] OKT3), phorbol myristate acetate (PMA), anti-CD3 and PMA, or 1% phytohemagglutinin (PHA) plus PMA. Analyses of the expression of IL-2R on activated T cells from elderly people revealed a marked heterogeneity in IL2R levels irrespective of the stimuli. Other experiments showed that the age-related alterations in surface expression of IL-2Ralpha were not correlated to changes in the release of soluble IL-2Ralpha. Age-related changes in IL-2R expression on activated T cells from individual donors were not coupled to the ability of the T cells to undergo G(1)/S progression. Collectively, these observations suggest that activated T cells from elderly people exhibit substantial heterogeneity in the expression of IL-2R subunits and that alterations in IL-2R expression may be distinct from intrinsic defects in G(1)/S progression and proliferative responses.
J Interferon Cytokine Res 2001 Jul
PMID:Alterations in the expression of interleukin-2R subunits by activated T cells from elderly humans are uncoupled from aberrancies in G1/S progression. 1150 46

Many studies illustrate that physical or psychologic stressors can alter human immune function, which might predispose one to an increased susceptibility to infections. In the present study, we monitored immune responsiveness in 16 first-year medical students (age 23.8 +/- 2.2 years) during the first examination session. Baseline blood samples were collected 30 days prior to the first examination session. Subsequently, subjects were randomly assigned to two groups, and blood samples were collected at 24 h (POST24h) or 48 h (POST48h) after an examination. The percentage of CD3(+), CD3(+)CD4(+), CD3(+)CD8(+), CD3(+)CD45RO(+), CD3(+)CD45RA(+), CD3(-)CD16(+)56(+), CD19(+), and CD14(+) cells in whole blood was examined to determine changes in circulating immune cell populations. Activation of peripheral blood mononuclear cells (PBMC) with a mixture of phorbol myristate acetate (PMA) and ionomycin or lipopolysaccharide (LPS) for 4 h was used to assess the distribution of interleukin-2 (IL-2)-secreting or interferon-gamma (IFN-gamma)-secreting CD4(+) and CD8(+) cells, as well as IL-1alpha-secreting CD14(+) cells. Activation with a combination of phytohemagglutinin (PHA) and LPS was used to assess secretion of IL-2, IFN-gamma, IL-4, IL-10, soluble IL-2 receptor-alpha (sIL-2Ralpha), IL-1beta, and IL-1R antagonist (IL-1Ra) by PBMC in 48-h cell culture. A significantly higher level of total T cells was found at POST24h, and CD14(+) was elevated at both POST24h and POST48h. The percentage of CD4(+) and CD8(+) cells significantly declined at POST24 and POST48h. A significant elevation in the percentage of memory T cells was observed at POST48h, whereas the percentage of naive T cells was elevated at POST24h and POST48h. These changes were accompanied by a significant decline in percentage of natural killer (NK) cells 24 h after the examination. The percentage of IL-2-producing CD4(+) and CD8(+) cells was significantly lower at POST24h, and the percentage of CD8(+)IFN-gamma(+) cells significantly declined at POST48h. The percentage of CD14(+)IL-1alpha(+) significantly declined at both POST24 and POST48h. A significant decrease was observed in IL-2 secretion 24 h after the examinations, and the secretion of IL-4 and IL-1beta significantly declined at POST48h. No changes in IFN-gamma, IL-10, sIL-2Ralpha, and IL-1Ra secretion were observed. We conclude that the stress outcomes of academic examinations in first-year medical students can significantly alter immune cell distribution and in vitro production and secretion of specific cytokines.
J Interferon Cytokine Res 2001 Sep
PMID:Immune responsiveness following academic stress in first-year medical students. 1157 63


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