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)

In murine acute viral myocarditis, natural killer (NK) cells infiltrate the heart first, followed by activated T-cells, which play an important role in the pathogenesis of the myocardial damage. Because of their multipotential effects, cytokines are thought to play a role in the induction and development of these immune processes. To clarify in more detail the precise mechanism of the cytokine networks involved, the expression of various cytokine mRNAs has been investigated in myocardial cells infected with Coxsackievirus B3 (CVB3) in vivo and in vitro by a semiquantitative polymerase chain reaction (PCR) method. Interleukin (IL)-1 alpha, IL-1 beta, IL-6, tumour necrosis factor (TNF)-alpha, and TNF-beta were expressed almost throughout the early phase of virus infection with some variations. IL-2, IL-3, IL-4, IL-10, interferon (IFN)-gamma, granulocyte/macrophage colony stimulating factor (GM-CSF), and IL-2 receptor (IL-2R) were mainly expressed by the infiltrating cells. TNF-alpha, TNF-beta, and IL-1 beta were also expressed partly by the infiltrating cells. T-helper (Th)1-related cytokines (IL-2, IFN-gamma, and TNF-beta) were more strongly expressed than Th2-related cytokines (IL-4 and IL-10) in vivo, indicating that the Th cells which infiltrated the heart and mediated the immune responses in the early phase of acute myocarditis were mainly of Th1-type.
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PMID:Expression of cytokine mRNAs in murine hearts with acute myocarditis caused by coxsackievirus b3. 937 Sep 55

Human T-cell leukemia virus type-I (HTLV-I), the etiologic agent of adult T-cell leukemia (ATL) transforms human T cells both in vivo and in vitro. However, the long latency period between infection and development of ATL, as well as the small fraction of the infected population that actually develops this disease, suggest that factors in addition to the virus are involved in its pathogenesis. Mutation of tumor suppressor gene p53 has been found in both HTLV-I-transformed T-cell lines and ATL cases at relatively low frequency. However, increasing evidence supports p53 functional impairment in HTLV-I-transformed T cells. Tax, the major transactivator of HTLV-I, is critical for the initial events involved in transformation. We have considered the possibility that p53 may regulate transcription of viral and cellular genes important for viral replication and transformation. Inactivation of p53 function might then permit constitutive expression of these viral and cellular genes. We have investigated the effects of wild-type and mutant p53 on Tax-mediated activation of the HTLV-I long terminal repeat (LTR) and the promoters of several cellular genes including the interleukin (IL)-1alpha, IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF ), and IL-2 receptor alpha chain gene. Jurkat, HuT78, and U937 cells were cotransfected with plasmids containing a chloramphenicol acetyltransferase (CAT ) reporter gene under viral or cellular promoter control and the Tax expression vector, in addition to vectors for a wild-type or mutant p53. Wild-type p53 is a potent repressor of viral and cellular activation by Tax. Mutations within p53 severely inhibit this downregulation. We also show that wild-type p53 suppresses transcription from the HTLV-I LTR in Jurkat-Tax, a T-cell line stably expressing Tax, and MT-2, a HTLV-I-transformed T-cell line. Wild-type, but not mutant, p53 interfered with the binding of TATA-binding protein (TBP) to the TATA motif of the HTLV-I LTR. These results suggest that p53 inactivation may lead to upregulation of viral and cellular genes and may also be important for establishment of productive viral infection and development of ATL.
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PMID:Repression of transcription from the human T-cell leukemia virus type I long terminal repeat and cellular gene promoters by wild-type p53. 938 10

Virus-associated hemophagocytic syndrome (VAHS) is a disorder characterized by benign generalized histiocytic proliferation and marked hemophagocytosis associated with systemic viral infection. An immunodeficiency which includes an extremely decreased leukocyte and platelet count together with abnormalities in the CD4/CD8 ratio are the most common features of VAHS. Here we report an early-onset periodontitis (EOP) patient with VAHS from the standpoint of host-parasite interaction to understand the effect of this systemic disorder which might possibly influence susceptibility to periodontal disease. The patient is a 16-year-old Japanese male clinically diagnosed as having generalized EOP with slight gingival inflammation and moderate bone loss. This patient manifested VAHS at 3 years of age, and then had an unusual 4 recurrences (at 5, 7, 11, and 14 years old). Laboratory tests conducted include: 1) complete blood analyses: 2) peripheral neutrophil functions (chemotaxis, phagocytosis, superoxide production, and adherence); 3) peripheral lymphocyte subpopulations and functions, T-cell proliferative activity and productivity of cytokines (interleukin-2 [IL-2], interferon gamma [IFN-gamma], and tumor necrosis factor alpha [TNF-alpha]); 4) serum cytokine levels (IL-1 beta, IL-2, soluble IL-2 receptor [sIL-2R], IL-4, IL-6, IFN-gamma, and TNF-alpha; 5) serum immunoglobulin G (IgG) antibody titers against periodontopathic bacteria; 6) serological human leukocyte antigen (HLA) typing; and 7) determination of bacterial flora of the periodontal pockets. The results indicated that the patient's neutrophil chemotaxis and random migration were below the normal range. In lymphocyte examinations, T-cell proliferative activity, IL-2, and IFN-gamma productivity were elevated. Serum IFN-gamma level was also significantly higher than normal range. No specific periodontopathic bacteria were predominant in the periodontal pockets, however, the serum IgG titer against Porphyromonas gingivalis was elevated throughout the examination period. It is suggested that VAHS might be a possible risk factor for periodontal disease, and hence may serve as a model in understanding the role of host defense mechanisms in the establishment of inflammatory periodontal disease.
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PMID:Host defensive, immunological, and microbiological observations of an early-onset periodontitis patient with virus-associated hemophagocytic syndrome. 944 99

Human T-cell lymphotropic virus type 1 (HTLV-1) is the etiologic agent of adult T-cell leukemia and HTLV-1-associated myelopathy. Novel, yet conserved RNA transcripts encoded from open reading frames (ORFs) I and II of the viral pX region are expressed both in vitro and in infected individuals. The ORF I mRNA encodes the protein p12(I), which has been shown to localize to cellular endomembranes, cooperate with bovine papillomavirus E5 in transformation, as well as bind to the IL-2 receptor beta and gamma chains and the H+ vacuolar ATPase. It is unknown what role p12(I) plays in the viral life cycle. Using an infectious molecular clone of HTLV-1 (ACH) and a derivative clone, ACH.p12(I), which fails to produce the p12(I) message, we investigated the importance of p12(I) in infected primary cells and in a rabbit model of the infection. ACH.p12(I) was infectious in vitro as shown by viral passage in culture and no qualitative or quantitative differences were noted between ACH and ACH.p12(I) in posttransfection viral antigen production. However, in contrast to ACH, ACH.p12(I) failed to establish persistent infection in vivo as indicated by reduced anti-HTLV-1 antibody responses, failure to demonstrate viral p19 antigen production in peripheral blood mononuclear cell (PBMC) cultures, and only transient detection of provirus by polymerase chain reaction in PBMC from ACH.p12(I)-inoculated rabbits. These results are the first to show the essential role of HTLV-1 p12(I) in the establishment of persistent viral infection in vivo and suggest potential new targets in antiviral strategies to prevent HTLV-1 infection.
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PMID:Selective ablation of human T-cell lymphotropic virus type 1 p12I reduces viral infectivity in vivo. 961 68

The Kampo (Japanese herbal) medicine, Sho-seiryu-to, which has traditionally been used for the treatment of colds and bronchial asthma, showed potent antiinfluenza A and B virus activity through augmentation of production of antiviral IgA antibody in the nasal and bronchoalveolar cavities of mice when administrated orally before viral infection. Sho-seiryu-to also showed antiinfluenza virus activity against A virus H1N1 subtype infected in aged mice (approximately 6 months old) with an increase of antiviral IgA antibody in the bronchoalveolar wash of the treated mice by similar administration. When mice infected with mouse nonadapted influenza A virus H3N2 subtype before 14 days were secondarily infected with mouse adapted A/PR/8 (H1N1) virus and administered Sho-seiryu-to orally after the second infection, replication of the virus in both nasal and bronchoalveolar cavities was significantly inhibited. Sho-seiryu-to had no effect on the mice which were not primed with mouse nonadapted virus when administered after the infection of mouse-adapted A/PR/8 virus. Oral administration of Sho-seiryu-to caused increment of viral-specific IgA antibody secreting cells in mouse nasal lymphocyte. Sho-seiryu-to also augmented IL-2 receptor beta chain+ T-cells in Peyer's patch of the infected mice. Sho-seiryu-to also significantly reduced viral titer in the nasal washes of the infected ovalbumin-sensitized bronchial asthma model mice. Oral administration of Sho-seiryu-to before and after vaccination significantly augmented hemagglutination-inhibiting antibody in the serum by nasal inoculation of influenza HA vaccine, and significantly augmented nasal antiviral IgA antibody and bronchoalveolar and serum antiviral IgG antibodies even after secondary vaccination although induction of antiviral antibody by intranasal vaccination was insufficient without Sho-seiryu-to. These results suggest that Sho-seiryu-to is able to prevent influenza virus infection by cross-protection of subtypes of influenza A virus and B virus. Sho-seiryu-to is also useful for the treatment of influenza virus infection in hosts with a history of influenza virus infection and/or influenza vaccination and allergic pulmonary inflammation, such as bronchial asthma, and can be used as an adjuvant to nasally inoculated influenza HA vaccine.
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PMID:In vivo antiinfluenza virus activity of Kampo medicine Sho-seiryu-to through mucosal immune system. 964 80

When BALB/c mice were treated with a Kampo (Japanese herbal) medicine "Sho-seiryu-to (SST)" (1 g/kg, 10 times) orally from 7 days before to 5 days after the infection and infected with mouse-adapted influenza virus A/PR/8/34 by nasal-site restricted infection, SST caused increment of the influenza virus hemagglutinin-specific IgA antibody secreting cells in nasal lymphocyte but not in Peyer's patch lymphocyte at 6 days after infection in comparison with water-treated mice. Oral administration of SST also augmented IL-2 receptor beta chain+ (activated) T-cell in Peyer's patch lymphocyte, but not in the nasal lymphocyte. We previously reported that SST showed potent anti-influenza virus activity through augmentation of the antiviral IgA antibody titer in the nasal and broncho-alveolar cavities of the mice (T. Nagai and H. Yamada, 1994, Int. J. Immunopharmacol. 16, 605-613). These results suggest that oral administration of SST shows anti-influenza virus activity in the nasal cavity by activation of T-cell in Peyer's patch lymphocyte and stimulation of production of anti-influenza virus IgA antibody in nasal lymphocyte. When ovalbumin-sensitized allergic pulmonary inflammation model mice were administered orally with SST (1 g/kg) from 8 days before (11 times) or from 2 h after (4 times) to 4 days after the infection and infected with mouse-adapted influenza virus A/PR/8/34, replications of the virus in the both nasal and broncho-alveolar cavities or only nasal cavity were significantly inhibited at 5 days after infection in comparison with water-treated control by augmenting antiviral IgA antibody, respectively. These results suggest that SST is useful for both prophylaxis and treatment of influenza virus infection on patients with allergic pulmonary inflammation, such as bronchial asthma.
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PMID:In vivo anti-influenza virus activity of Kampo (Japanese herbal) medicine "sho-seiryu-to"--stimulation of mucosal immune system and effect on allergic pulmonary inflammation model mice. 965 72

AY 9944 [AY; trans-1,4-bis(chlorobenzylaminomethyl)-cyclohexane dihydrochloride], an inhibitor of sterol synthesis, was found to help restore the normal mitogenic responses and cytokine profiles of peripheral mononuclear cells (PBMCs) from AIDS patients in vitro. Compared to untreated cells, the human immunodeficiency virus type 1 (HIV-1)-infected PBMCs precultured in the presence of AY exhibited a normal rate of either mitogen-induced or recall- and superantigen-induced proliferation. After 2 weeks in the presence of the drug, the percentage of dead CD4(+) cells in HIV-1-infected cultures was comparable to that observed in uninfected cultures, while over the same time interval it increased by three- to fivefold in HIV-1-infected cultures maintained in the absence of AY. AY also stimulated by 2- to 12-fold interleukin-12 (IL-12) and (gamma interferon production. For IL-12, this effect appears to be related to an increase in corresponding IL-12 p35 and IL-12 p40 mRNA levels. Moreover, AY restored the expression of the IL-2 receptor, which was severely impaired in HIV-1-infected PBMCs. Although the drug has no direct antiviral effect (it does not significantly inhibit reverse transcriptase activity measured in vitro), it might be considered a potential therapeutic agent for HIV-infected patients, in that it may correct viral infection-related immune system defects by indirectly enhancing the level of resistance to HIV and opportunistic infections.
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PMID:Restoration of immune response by a cationic amphiphilic drug (AY 9944) in vitro: a new approach To chemotherapy against human immunodeficiency virus type 1. 975 45

Murine gammaherpesvirus 68 (MHV68) establishes long-term latency in memory B cells similar to the human gammaherpesvirus Epstein Barr Virus (EBV). EBV encodes an interleukin-10 (IL-10) homolog and modulates cellular IL-10 expression; however, the role of IL-10 in the establishment and/or maintenance of chronic EBV infection remains unclear. Notably, MHV68 does not encode an IL-10 homolog, but virus infection has been shown to result in elevated serum IL-10 levels in wild-type mice, and IL-10 deficiency results in decreased establishment of virus latency. Here we show that a unique MHV68 latency-associated gene product, the M2 protein, is required for the elevated serum IL-10 levels observed at 2 weeks post-infection. Furthermore, M2 protein expression in primary murine B cells drives high level IL-10 expression along with increased secretion of IL-2, IL-6, and MIP-1alpha. M2 expression was also shown to significantly augment LPS driven survival and proliferation of primary murine B cells. The latter was dependent on IL-10 expression as demonstrated by the failure of IL10-/- B cells to proliferate in response to M2 protein expression and rescue of M2-associated proliferation by addition of recombinant murine IL-10. M2 protein expression in primary B cells also led to upregulated surface expression of the high affinity IL-2 receptor (CD25) and the activation marker GL7, along with down-regulated surface expression of B220, MHC II, and sIgD. The cells retained CD19 and sIgG expression, suggesting differentiation to a pre-plasma memory B cell phenotype. These observations are consistent with previous analyses of M2-null MHV68 mutants that have suggested a role for the M2 protein in expansion and differentiation of MHV68 latently infected B cells-perhaps facilitating the establishment of virus latency in memory B cells. Thus, while the M2 protein is unique to MHV68, analysis of M2 function has revealed an important role for IL-10 in MHV68 pathogenesis-identifying a strategy that appears to be conserved between at least EBV and MHV68.
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PMID:The MHV68 M2 protein drives IL-10 dependent B cell proliferation and differentiation. 1838 62

This randomized, pilot study compared the Janus kinase inhibitor CP-690,550 (15 mg BID [CP15] and 30 mg BID [CP30], n = 20 each) with tacrolimus (n = 21) in de novo kidney allograft recipients. Patients received an IL-2 receptor antagonist, concomitant mycophenolate mofetil (MMF) and corticosteroids. CP-690,550 doses were reduced after 6 months. Due to a high incidence of BK virus nephropathy (BKN) in CP30, MMF was discontinued in this group. The 6-month biopsy-proven acute rejection rates were 1 of 20, 4 of 20 and 1 of 21 for CP15, CP30 and tacrolimus groups, respectively. BKN developed in 4 of 20 patients in CP30 group. The 6-month rates of cytomegalovirus disease were 2 of 20, 4 of 20 and none of 21 for CP15, CP30 and tacrolimus groups, respectively. Estimated glomerular filtration rate was >70 mL/min at 6 and 12 months (all groups). NK cells were reduced by </=77% in CP-690,550-treated patients. In the CP-690,550 arms, there were modest lipid elevations and a trend toward more frequent anemia and neutropenia during the first 6 months. These data suggest that coadministration of CP-690,550 30 mg BID with MMF is associated with overimmunosuppression. At 15 mg BID, the efficacy/safety profile was comparable to the tacrolimus control group, excepting a higher rate of viral infection. Further dose-ranging evaluation of CP-690,550 is warranted.
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PMID:Calcineurin-inhibitor-free immunosuppression based on the JAK inhibitor CP-690,550: a pilot study in de novo kidney allograft recipients. 1966 21

CD25, the high-affinity interleukin-2 (IL-2) receptor alpha chain, is rapidly upregulated by antigen-specific CD8(+) T cells after T cell receptor stimulation. Here, we demonstrate that during an acute viral infection, CD25 expression is quite dynamic-after initial upregulation, a subset of virus-specific T cells sustains CD25 expression longer than the rest. At this time when there is distinct heterogeneity in CD25 expression, examination of the in vivo fate of effector cells revealed that CD25(lo) cells, which are relatively less sensitive to IL-2, preferentially upregulate CD127 and CD62L and give rise to functional long-lived memory cells. In contrast, CD25(hi) cells perceiving prolonged IL-2 signals proliferate more rapidly, are prone to apoptosis, exhibit a more pronounced effector phenotype, and appear to be terminally differentiated. Consistent with this, sustained IL-2 receptor signaling during expansion drove terminal-effector differentiation. These data support the hypothesis that prolonged IL-2 signals during priming promote terminal-effector differentiation.
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PMID:Prolonged interleukin-2Ralpha expression on virus-specific CD8+ T cells favors terminal-effector differentiation in vivo. 2009 8


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