UNIPROT:P14784 - FACTA Search

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Query: UNIPROT:P14784 (IL-2 receptor)
3,849 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Trypanosoma cruzi infection in humans and experimental animals often results in a chronic heart and gut inflammation and a dysfunction known as Chagas' disease. Previous studies have shown that the cellular infiltrate in the hearts of animals with chronic Chagas' disease consists mainly of CD8+ T cells. In this study, we have used immunohistochemical techniques to further characterize the immunological nature of chagasic heart lesions in three murine models of experimental Chagas' disease. Double-staining immunohistochemistry revealed that 10-30% of the infiltrating CD8+ T cells in the hearts of infected mice expressed the activation molecules, IL-2 receptor and CD44. In addition, large numbers of cells producing TNF-alpha, TGF-beta, IL-1 alpha, and IL-6 were consistently observed in the heart lesions, appearing during the acute infection and persisting throughout the chronic stage of infection (> 300 days). In contrast, IFN-gamma- and IL-10-producing cells were detected in relatively low numbers and only transiently between approximately 3 and 9 weeks postinfection. Cells producing IL-2, IL-4, and IL-5 were not observed in the hearts of mice at any point during the infection. The appearance of cytokine-producing cells in the hearts correlated with an increased local expression of class I and class II MHC molecules and adhesion molecules (ICAM-1, LFA-1, VLA-4, and VCAM-1). The results of this study suggest that the chronic inflammation in chagasic hearts is highly active and associated with a stable immunological pattern extending from the early acute stage of the infection through the late chronic stage. The pattern of cytokine production in heart is distinct from that observed in lymphoid organs and is not suggestive of an association between particular classes of cytokines and disease development. Instead it appears that both inflammatory and anti-inflammatory cytokines determine the pattern of the cellular response and the severity of disease in T. cruzi infection.
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PMID:Persistent production of inflammatory and anti-inflammatory cytokines and associated MHC and adhesion molecule expression at the site of infection and disease in experimental Trypanosoma cruzi infections. 893 70

Cellular and mediator profiles in bronchoalveolar lavage have not been compared systematically between patients with asthma of different severities, mainly because the patients with more severe asthma have an increased need for antiinflammatory medication. Information is limited to comparisons of allergic and intrinsic asthma, which can be distinguished clinically. When patients from these two groups with similar degrees of bronchial hyperresponsiveness were compared, both groups showed increased numbers of activated T-helper lymphocytes; those in the allergic group expressed the IL-2 receptor (CD25+), whereas in patients with intrinsic asthma there was also an increased number of T-suppressor cells with the activation markers CD25, class II histocompatibility antigen, and very late activation antigen-I, as well as T-helper cells class II histocompatibility antigen and very late activation antigen-I. This pattern is compatible with a more chronic T-cell activation in patients with intrinsic asthma. In patients with allergic asthma the cytokine pattern is compatible with a pure TH2 response (elevated IL-4 and IL-5); however, intrinsic asthma is characterized by elevated IL-5 and IL-2 but not IL-4. Our own findings show similar concentrations of IL-1, IL-8, and granulocyte-macrophage colony-stimulating factor in bronchoalveolar lavage fluid of patients with allergic and intrinsic asthma, whereas IL-6 and interferon-gamma tended to be higher in patients with intrinsic asthma. There are probably fundamental differences in the pathogenesis of allergic and intrinsic asthma. These findings suggest that asthma does not depend on the presence of IgE or IL-4, although both may contribute to the pathogenesis of atopic asthma. The only common pathway in the different presentations of asthma that has been related to clinical symptoms appears to be IL-5-mediated activation of eosinophils; therapies aimed at this mechanism may be promising.
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PMID:Inflammatory determinants of asthma severity: mediator and cellular changes in bronchoalveolar lavage fluid of patients with severe asthma. 893 74

According to the widely accepted classification, human TH cell clones can be divided into two mutually exclusive subsets, TH1 and TH2, based on their profile of cytokine production. The intracellular difference between these clones is not clear. To characterize the biochemical nature of T-cell receptor (TCR)/CD3 complex-mediated signal transduction pathways, we introduced several human TH cell clones of THO- or TH1-like phenotype and analyzed the effects of various drugs and antibodies on cytokine production or proliferation of these clones. The tyrosine kinase inhibitor herbimycin inhibited the production of interferon-gamma (IFN-gamma) by THO-like clone, after stimulation with anti-CD3 monoclonal antibody alpha CD3-mAb) or with phorbol 12-myristate 13-acetate (PMA) and the calcium ionophore A23187. However, whereas herbimycin strongly inhibited the production of IL-4 and IL-5 by alpha CD3 mAb stimulated T cells, it did not affect the production of these cytokines after PMA/A23187 stimulation. Cyclosporin A inhibited the proliferation as well as the production of the cytokines, including that of IL-2, IL-4, IL-5, and IFN-gamma, irrespective of the mode of stimulation. A23187, which synergizes with PMA in the induction of IL-4 and IFN-gamma, inhibited PMA-induced IL-10 production in a dose-dependent manner. Transforming growth factor-beta and anti-IL-2 receptor monoclonal antibody partially inhibited alpha CD3 mAb-mediated T-cell proliferation, but had no effect on the proliferation induced by PMA and A23187. Cyclic adenosine monophosphate (cAMP)-elevating drugs, like prostaglandin E2 and dibutyryl cAMP, inhibited the TCR-mediated cytokine production but shifted the cytokine production profile from a TH0 to a TH2 type after stimulation with PMA and A23187. Finally, we analyzed the induction of activity of two transcription factors, nuclear factor-kappa B (NF-kappa B) and nuclear factor of activated T cells, involved in the regulation of cytokine gene expression, after a different mode of activation. The induction of NF-kappa B (p50/p65 heterodimer) by using alpha CD3-mAb stimulation but not by using PMA/A23187 stimulation was found to be inhibited by using cAMP-elevating drugs.
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PMID:Factors affecting the cytokine production of human T cells stimulated by different modes of activation. 897 24

Sclerosing keratitis is the major cause of blindness due to onchocerciasis which results from chronic infection with the filarial parasite Onchocerca volvulus. Using a murine model of onchocercal sclerosing keratitis, we have demonstrated previously that predominantly (> 85%) CD3 + /CD4+ T-cells as well as the IL-2 receptor bearing cells infiltrate into the cornea in vivo during development and progress of the disease. The identification of CD4+ subsets TH1 and TH2 based on the cytokine secretion patterns of murine T-lymphocytes has been useful for understanding the immune basis of resistance and pathogenesis in murine models of several parasitic diseases. The present investigation was carried out to demonstrate whether the local immune response at the corneal lesion due to onchocercal interstitial keratitis correlated with such distinct patterns of cytokine production. For that purpose, mRNA was extracted separately from corneas obtained from the diseased eyes and the normal eyes of A/J mice with onchocercal interstitial keratitis, reverse transcribed and amplified by the polymerase chain reaction with four different cytokine specific primers. In corneas obtained from the eyes affected with onchocercal interstitial keratitis, mRNAs coding for IL-4 and IL-5 were up-regulated compared to the normal eyes having no lesions from the same animals. However, the levels of mRNAs for IL-2 and IFN gamma were found to be the same in the diseased and normal eyes. Taken together, these data suggest that IL-4 and IL-5 producing TH2-lymphocytes are active at the corneal lesion due to onchocercal interstitial keratitis.
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PMID:In vivo molecular analysis of cytokines in a murine model of ocular onchocerciasis. I. Up-regulation of IL-4 and IL-5 mRNAs and not IL-2 and IFN gamma mRNAs in the cornea due to experimental interstitial keratitis. 903 Sep 83

Regulation of T cell IL-5 synthesis was investigated using human Th cell clones. Immunosuppressant FK506 suppressed IL-5 synthesis of T cells activated through TCR in a dose-dependent manner. IL-5 gene transcription and protein synthesis were also induced in the same T cell clones upon stimulation with IL-2 and were suppressed by FK506 in a dose response similar to that induced by TCR stimulation. In contrast to TCR stimulation, neither activating protein-1, nuclear factor-AT (NF-AT), nor NF-kappaB binding activity was significantly up-regulated by IL-2 stimulation. Human IL-5 promoter/enhancer-luciferase gene construct transfected to T cell clones was transcribed upon either TCR or IL-2 stimulation and was clearly down-regulated by FK506, indicating that the approximately 500-bp human IL-5 gene segment located 5' upstream of the coding region contained FK506-sensitive enhancer elements. Our present findings clearly indicate that FK506-sensitive signaling molecules are involved in T cell IL-5 production induced by both TCR and IL-2 stimulation and suggest that IL-2 receptor signal leading to IL-5 gene transcription is transduced by a unique FK506-sensitive pathway other than the Ca2+-dependent signal transduction pathway, such as the calcineurin-NF-AT system.
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PMID:IL-2-induced IL-5 synthesis, but not proliferation, of human CD4+ T cells is suppressed by FK506. 910 28

Glucocorticoids (GC) have long been used as the most effective agents for the treatment of allergic diseases accompanied by eosinophilia such as chronic asthma and atopic dermatitis. The development of chronic eosinophilic inflammation is dependent on interleukin-5 (IL-5), a selective eosinophil-activating factor, produced by helper T cells. To delineate the regulatory mechanisms of human IL-5 synthesis, we established allergen-specific CD4+ T-cell clones from asthmatic patients. GC efficiently suppressed IL-5 synthesis of T-cell clones activated via either T-cell receptor (TCR) or IL-2 receptor (IL-2R). Induction of IL-5 mRNA upon TCR and IL-2R stimulation was totally inhibited by dexamethasone. Human IL-5 promoter/enhancer-luciferase gene construct transfected to T-cell clones was transcribed on either TCR or IL-2R stimulation and was clearly downregulated by dexamethasone, indicating that the approximately 500-bp human IL-5 gene segment located 5' upstream of the coding region contains activation-inducible enhancer elements responsible for the regulation by GC. Electrophoretic mobility shift assay analysis suggested that AP-1 and NF-kappaB are among the possible targets of GC actions on TCR-stimulated T cells. NF-AT and NF-kappaB were not significantly induced by IL-2 stimulation. Our results showing that GC suppressed IL-5 production by human CD4+ T cells activated by two distinct stimuli, TCR and IL-2R stimulation, underscore the efficacy of GC in the treatment of allergic diseases via suppression of T-cell IL-5 synthesis.
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PMID:Two distinct pathways of interleukin-5 synthesis in allergen-specific human T-cell clones are suppressed by glucocorticoids. 910 9

T cell cytokine expression may be induced by the cytokine IL-2 or via the TCR complex. The comparative effects of cytokine- and TCR-mediated signalling on the induction of human IL-5 mRNA were examined. Cytokine mRNA expression was analysed by RT-PCR in fresh peripheral blood mononuclear cells (PBMC) from normal individuals and in populations of activated T lymphocytes, derived from phytohaemagglutinin (PHA)-stimulated PBMC. rIL-2 induced IL-5 expression in PBMC, the kinetics of which were similar to the effects of PHA. rIL-4 induced IL-5 mRNA expression in activated T lymphocytes. IL-5 expression induced by either IL-2 or PHA was completely abolished by the protein synthesis inhibitor cycloheximide. rIL-2-induced IL-5 expression was resistant to cyclosporin A (CsA), whereas IL-5 expression elicited by PHA was inhibited by CsA, at doses as low as 10 ng/ml. Rapamycin (RAP) had no effect on rIL-2-stimulated IL-5 expression, but suppressed IL-5 expression induced by PHA. The inhibitory effect of RAP on PHA-induced IL-5 expression was more apparent at 12 and 24 h after stimulation than at earlier times. The resistance of IL-2 receptor (IL-2R) signalling to CsA and RAP indicates that the IL-2R and the TCR are associated with different pathways regulating IL-5 expression.
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PMID:Induction of IL-5 expression by IL-2 is resistant to the immunosuppressive agents cyclosporin A and rapamycin. 923 6

Subjects with generalized onchocerciasis (GEN), with the sowdah form, and with exposure but without onchocerciasis (endemic normal/putatively immune; EN/PI) were studied for cytokine responses to Onchocerca volvulus extract (OvAg) and recombinant Ov33 and OvL3-1 proteins. Higher levels of cytokines were produced in response to OvAgs in sowdah and EN/PI than in GEN subjects. Peripheral blood mononuclear cells did not produce interferon-gamma in response to antigens. OvAg induced interleukin (IL)-5, IL-2, granulocyte-macrophage colony-stimulating factor (GM-CSF), and soluble IL-2 receptor. EN/PI and sowdah persons produced significantly more IL-5 and IL-2 than GEN subjects, and EN/PI subjects had significantly higher GM-CSF levels than GEN persons. The low IL-5 and GM-CSF levels in GEN subjects were increased by addition of exogenous IL-2. Ov33 and OvL3-1 stimulated production of IL-10 and less IL-5 and IL-2. The study groups did not show a strict Th2-like cytokine response.
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PMID:Differences in cytokine responses to Onchocerca volvulus extract and recombinant Ov33 and OvL3-1 proteins in exposed subjects with various parasitologic and clinical states. 929 49

Semi-quantitative, polymerase chain reaction (PCR) is used to uncover the patterns of cytokine transcription in the mouse thymus from day 14 to day 20 of gestation, a time period which includes many of the important events in thymic ontogeny. Interleukin 4 (IL-4), IL-7 and interferon gamma (IFN-gamma) mRNA is abundant from fetal day (Fd) 14-16, corresponding with the period of rapid proliferation of immature thymocytes in vivo. As the level of mRNA for these cytokines diminishes, the induction and increased expression of IL-3 and IL-2 occurs. The transcription of these cytokines correlates temporally with the period of proliferation-dependent phenotypic differentiation between Fd 16 and 20. The thymic epithelium (TE)-derived cytokines including IL-1alpha, IL-6 and granulocyte-macrophage colony-stimulating factor (GM-CSF) begin to be transcribed between Fd 14-15 and show peak mRNA abundance from Fd 16-20. IL-5, tumour necrosis factor alpha (TNF-alpha) and LT (lymphotoxin or TNF-beta) constitute a fourth group of cytokines, along with the IL-4 receptor (IL-4R), which are transcribed at an even level throughout the fetal period. The IL-2 receptor beta chain (IL-2Rbeta) and IL-10 show abundant mRNA from Fd 14-20 and have a peak level of mRNA content on Fd 16. Taken together, these studies uncover complex, overlapping patterns of cytokine gene expression. The mRNA abundance and pattern of expression of each cytokine or cytokine receptor may indicate the relative contribution that it makes to different stages of fetal thymic ontogeny.
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PMID:Semi-quantitative polymerase chain reaction analysis of cytokine and cytokine receptor gene expression during thymic ontogeny. 934 2

Some cytokines have been suggested to take part in the blister formation in bullous pemphigoid (BP). However, the roles of the cytokines are only partly understood. To elucidate the involvement of cytokines in the immunological mechanisms in BP, we investigated the serum levels of interleukin (IL)-2, IL-4, IL-5, IL-6, IL-8, IL-13, soluble IL-2 receptor and soluble CD23 in patients with BP, and the correlation between cytokine levels and other clinical and laboratory data. Serum levels of these cytokines and soluble receptors were determined by enzyme-linked immunosorbent assay in 19 patients with BP and in 16 normal control subjects. Serum levels of IL-5 (P < 0.0001), IL-6 (P < 0.01) and IL-8 (P < 0.05) were significantly higher in BP patients than in the control subjects. Other cytokines and soluble receptor levels were not significantly different. Serum levels of IL-6 (P < 0.05) and IL-8 (P < 0.05) were significantly decreased after treatment when skin lesions disappeared. These results suggest that serum levels of IL-6 and IL-8 could be indicators of disease activity of BP.
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PMID:Increased serum levels of interleukin (IL)-5, IL-6 and IL-8 in bullous pemphigoid. 945 28

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