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Uso de IL-2 humana recombinante em pacientes com imunodeficiência comum variável; Use of recombinant human IL-2 in patients with common variable immunodeficiency

Narciso, João Henrique Fagundes Bastos
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Dissertação de Mestrado Formato: application/pdf
Publicado em 06/05/2008 PT
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Na imunodeficiência comum variável (ICV) têm sido descritas alterações de linfócitos T, incluindo a produção diminuída da interleucina-2 (IL-2). Desde que a IL-2 pode promover a produção de imunoglobulinas in vitro, nosso principal objetivo foi investigar os efeitos in vivo do tratamento com IL-2 recombinante (IL-2r) em pacientes com ICV. Foram selecionados 4 pacientes que apesar de tratamento adequado com imunoglobulina EV apresentavam infecções recorrentes. Após um período de observação de 12 meses, os pacientes receberam doses crescentes de IL-2r durante 16 semanas com reposição de imunoglobulina apenas se a IgG sérica atingisse níveis menores do que 400mg/dL. A seguir, permaneceram em observação por mais 12 meses recebendo imunoglobulina . A gravidade das infecções foi avaliada segundo um "score" numa escala de 3 a 10. A avaliação in vitro incluiu: quantificação dos níveis de IgG, IgA e IgM séricas; resposta linfoproliferativa à PHA; populações linfocitárias CD4+, CD8+, CD19+ e CD25+ no sangue periférico. As reações adversas à IL-2r foram leves e localizadas. Houve redução aparente do número e gravidade das infecções durante os 12 meses subseqüentes ao término da IL-2r. Os níveis da IgG sérica e das células CD4+...

Efeitos da administração de interleucina-2 na liberação in vivo de dopamina no nucleus accumbens e no comportamento maternal em ratas; Effects of interleukin-2 administration on nucleus accumbens dopamine levels and maternal behavior in rats.

Habr, Soraya Ferreira
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Tese de Doutorado Formato: application/pdf
Publicado em 08/12/2008 PT
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A interleucina-2 (IL-2) atua na modulação da atividade dopaminérgica, que influencia o comportamento maternal. Neste estudo observou-se que o estado lactacional reduziu a atividade geral em campo aberto, porém não alterou os níveis de dopamina e seus metabólitos. A administração de IL-2, tanto sistêmica com diretamente no N.Ac não alterou a atividade geral em campo aberto, indicando a ausência de efeito motor da mesma. Além disso, a administração de IL-2 sistêmica e no N.Ac reduziu as porcentagens de ratas que agrupam os filhotes e de filhotes agrupados por rata. A injeção de IL-2 no N.Ac aumentou as latências de busca do primeiro e segundo filhotes e o comportamento agressivo. A administração sistêmica de IL-2 em ratas virgens reduziu somente do valor absoluto de DOPAC (metabólito de dopamina) após 100 e 120. Este achado corrobora a idéia de que o IL-2 altera a atividade dopaminérgica. Os resultados sugerem que a administração sistêmica da dose de IL-2 estudada não influencia de forma significativa os níveis de dopamina e de seus metabólitos no N.Ac.; Interleukin-2 (IL-2) modulates the dopaminergic neurotransmission, that into the nucleus accumbens (N.Ac) plays a role in maternal behavior. The IL-2 dose used in this study does not have motor effects. Both peripheral and central N.Ac injections decreased the percent of mothers grouping pups together and the number of grouped pups. IL-2 injections into the N.Ac resulted in longer latencies to retrieve first and second pups and increased aggressive behavior. In order to test if these behavioral effects would be related to the IL-2 reduced the DOPAC (dopamine metabolite) concentrations in the N.Ac of virgin rats treated with IL-2. This suggests suggest that the IL-2 dose used in this study does not alter so much the dopaminergic transmission by influencing extracellular levels of this neurotransmitter.

Construção e caracterização in vitro  de um vetor retroviral bicistrônico codificando endostatina e interleucina-2 para utilização em terapia gênica; Construction and chracterization in vitro of a bicistronic retroviral vector coding endostatin and interleukin-2 for use in gene therapy

Calvo, Fernanda Bernardes
Fonte: Biblioteca Digitais de Teses e Dissertações da USP Publicador: Biblioteca Digitais de Teses e Dissertações da USP
Tipo: Dissertação de Mestrado Formato: application/pdf
Publicado em 09/12/2009 PT
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A terapia gênica tem sido empregada em estudos pré-clínicos e clínicos, com o intuito de amenizar ou curar uma doença. Vetores retrovirais são uma ferramenta de transferência gênica largamente utilizada. Vetores bicistrônicos são uma alternativa interessante para o tratamento de doenças complexas. Na construção de um vetor bicistrônico pode-se empregar várias estratégias dentre elas a utilização da sequência IRES. A endostatina, fragmento do colágeno XVIII, tem sido muito utilizada na terapia anti-angiogênica devido sua ação inibitória no crescimento de células endoteliais. A imunoterapia tem sido utilizada como tratamento coadjuvante de tumores. Dentre as citocinas utilizadas, a interleucina-2 promovendo a proliferação de linfócitos T, tem sido utilizada em diversos estudos pré-clínicos e clínicos. O objetivo deste projeto foi construir e caracterizar in vitro um vetor retroviral bicistrônico codificando endostatina e interleucina-2 utlizando a sequência IRES. A construção do vetor foi realizada em três etapas, sendo comprovada a construção final por análise de restrição e seqüenciamento. Células de empacotamento foram transfectadas com o vetor, e posteriormente realizada a transdução na célula alvo. A endostatina e a interleucina-2 foram determinadas por Dot blot...

Interleukin-2 and interleukin-6 gene promoter polymorphisms, and early failure of dental implants

Campos, Maria Isabela Guimarães; Godoy Dos Santos, Maria Cristina Leme; Trevilatto, Paula Cristina; Scarel-Caminaga, Raquel Mantuaneli; Bezerra, Fabio Jose; Line, Sergio Roberto Peres
Fonte: Universidade Estadual Paulista Publicador: Universidade Estadual Paulista
Tipo: Artigo de Revista Científica Formato: 391-398
ENG
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Single nucleotide polymorphisms in the promoter region of the human interleukin (IL)-2 (T-330G) and IL-6 (G-174C) genes have modified the transcriptional activity of these cytokines and are associated with several diseases. The aim of this study was to investigate the possible relationship between these single nucleotide polymorphisms and early implant failure. A sample of 74 nonsmokers was divided into 2 groups: test group comprising 34 patients (mean age 49.3 years) with ĝ‰¥1 implants that failed and control group consisting of 40 patients (mean age 43.8 years) with ĝ‰¥1 healthy implants. Genomic deoxyribonucleic acid from oral mucosa was amplified by polymerase chain reaction and analyzed by restriction fragment length polymorphism. Monte Carlo simulations (P < 0.05) were used to assess differences in allele and genotypes frequencies of the single nucleotide polymorphisms between the 2 groups. No significant differences were observed in the allele and genotypes distribution of both polymorphisms when the 2 groups were compared. The results indicate that polymorphisms in the IL-2 (T-330G) and IL-6 (G-174C) genes are not associated with early implant failure, suggesting that the presence of those single nucleotide polymorphisms does not constitute a genetic risk factor for implant loss in the studied population. Copyright © 2005 by Lippincott Williams & Wilkins.

Interleukin- 2 production during murine infection by Leishmania mexicana amazonensis

Barral-Netto,Manoel; Roters,Silene B.; Barral,Aldina
Fonte: Instituto Oswaldo Cruz, Ministério da Saúde Publicador: Instituto Oswaldo Cruz, Ministério da Saúde
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/03/1986 EN
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Highly susceptible BALB/c mice, resistant C57B1/6 and their F1 progeny (BDF1) were infected subcutaneously in the foot pad with Leishmania mexicana amazonenesis. At various times after infection, spleen or draining popliteal lymph node cells were assayed for their capacity to generate Interleukin-2 (I1-2) by Concanavalin A (ConA) stimulation. In both BALB/c and C57B1/6 strains there was a transient increase in their capacity to produce I1-2, from the 3rd to the 10th week post-infection. Return to pre-infection levels ocurred between 13th to 16th week post-infection in all three strains. BALB/c mice always produced higher titers of 11-2 than C57B1/6, but such differences were statistically significant only at 3 and 10 weeks post-infection. BDF1 mice had titers similar to those observed in BALB/c mice. I1-2 production by ConA-stimulated lymph node cells was lower as compared to the spleen, but with a similar pattern among the three mice strains. Our data show that susceptibility to infection by l. mexicana amazonenesis is not associated with deficient ConA-stimulated I1-2 production.

The effect of medium composition on interleukin-2 production by murine EL-4 thymoma cells

Galesi,A. L. L.; Tamashiro,W. M. S. C.; Moraes,A. M.
Fonte: Brazilian Society of Chemical Engineering Publicador: Brazilian Society of Chemical Engineering
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/06/2004 EN
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Due to the role of interleukin-2 (IL-2) in the mediation of immune response, this cytokine has been used in the treatment of some types of cancer and infectious diseases. However, relatively high levels of this cytokine are required to achieve significant activity. The aim of this work was to study a culture medium composition designed to increase the production of IL-2 by suspended murine EL-4 cells. The cultivations were carried out aiming at producing IL-2 in stirred bioreactors. The effects of concentration of glutamine, phorbol-12-myristate-13-acetate (PMA), concanavalin A (Con A), Pluronic F68, and fetal calf serum (FCS) on cell viability and IL-2 production were evaluated. PMA alone was more efficient in IL-2 production than it was in association with Con A. The maximum IL-2 production was around 162 ng/mL with 856 ng/mL PMA and 1.45% (v/v) FCS.

Direct evidence that ERK regulates the production/secretion of interleukin-2 in PHA/PMA-stimulated T lymphocytes

Li, Y.; Hii, C.; Der, C.; Ferrante, A.
Fonte: BLACKWELL SCIENCE LTD Publicador: BLACKWELL SCIENCE LTD
Tipo: Artigo de Revista Científica
Publicado em //1999 EN
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Although p21ras, raf-1 and MEK have been shown to regulate directly the transcriptional activity of NFAT (nuclear factor of activated T cells) and/or the interleukin-2 (IL-2) promoter, direct evidence that the extracellular signal-regulated protein kinase (ERK) is involved in regulating IL-2 production is still lacking. Here, we demonstrate that transfection of Jurkat cells with a dominant negative mutant of ERK1 (Erk1-K71R) resulted in the suppression of mitogen-stimulated production/secretion of IL-2. This was accompanied by a parallel inhibition of mitogen-stimulated ERK activity. These data provide direct evidence, for the first time, that ERK plays a vital role in regulating the production/secretion of IL-2.

Reduced expression of the interleukin-2-receptor gamma chain on cord blood lymphocytes: relationship to functional immaturity of the neonatal immune response

Zola, H.; Fusco, M.; Weedon, H.; Macardle, P.; Ridings, J.; Roberton, D.
Fonte: BLACKWELL SCIENCE LTD Publicador: BLACKWELL SCIENCE LTD
Tipo: Artigo de Revista Científica
Publicado em //1996 EN
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Mutation of the interleukin-2 (IL-2) receptor gamma chain, which also serves as a component of the receptor complexes for IL-4, 7, 9 and 15, results in severe immune deficiency. We hypothesized that the immunological immaturity of healthy neonates might be associated with low levels of expression of this receptor molecule. Using monoclonal antibody and a highly sensitive immunofluorescence method, we showed that IL-2 receptor gamma chain is expressed at significantly lower levels on cord blood cells compared with adult cells. IL-2-dependent T-cell activation in vitro was reduced in cord blood cells compared with adult cells, but B-cell responses to IL-4 were not obviously impaired. The lower level of expression of the gamma chain and some other cytokine receptor chains may contribute to the immunological immaturity of the newborn, by selectively depressing particular immunological mechanisms.

Interleukin-2 in human milk: A potential modulator of lymphocyte development in the breastfed infant

Bryan, D.L.; Forsyth, K.; Gibson, R.; Hawkes, J.
Fonte: Academic Press Ltd Elsevier Science Ltd Publicador: Academic Press Ltd Elsevier Science Ltd
Tipo: Artigo de Revista Científica
Publicado em //2006 EN
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Development of lymphocyte subpopulations and response to antigen exposure will be influenced by the limited ability of neonates to produce cytokines. In the case of cytokines such as interleukin (IL)-2 which are potent T lymphocyte regulators but poorly produced by newborn infants, the supply of cytokines through human milk could alleviate an immunological deficit and potentially aid the maturation of the immune system. We analysed human milk from 52 mothers (15–357 days postpartum) by ELISA to determine levels of aqueous IL-2, as well as production by human milk cells. IL-2 was detectable (>8 pg/mL) in the aqueous phase of 81% of all day 1 samples with no significant difference found in the mean concentration over 3 consecutive days. IL-2 was produced constitutively at detectable levels by 57% of milk cell samples and production was significantly increased by stimulation with Con A (380%). No correlation was found between aqueous and cellular IL-2, however there was a significant correlation between milk aqueous IL-2 and serum IL-2. This is the first report of IL-2 in the aqueous phase of human milk. A supply of exogenous IL-2 in human milk may provide the suckling infant with important immunological signals during a significant stage of T cell development.; http://www.elsevier.com/wps/find/journaldescription.cws_home/622815/description#description; Dani-Louise Bryan...

The 20th anniversary of interleukin-2 therapy: Bimodal role explaining longstanding random induction of complete clinical responses

Coventry, B.; Ashdown, M.
Fonte: Dove Medical Press Ltd Publicador: Dove Medical Press Ltd
Tipo: Artigo de Revista Científica
Publicado em //2012 EN
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Background: This year marks the twentieth anniversary of the approval by the US Food and Drug Administration of interleukin-2 (IL2) for use in cancer therapy, initially for renal cell carcinoma and later for melanoma. IL2 therapy for cancer has stood the test of time, with continued widespread use in Europe, parts of Asia, and the US. Clinical complete responses are variably reported at 5%–20% for advanced malignant melanoma and renal cell carcinoma, with strong durable responses and sustained long-term 5–10-year survival being typical if complete responses are generated. Methods: The literature was reviewed for the actions and clinical effects of IL2 on subsets of T cells. The influence of IL2 on clinical efficacy was also sought. Results: The review revealed that IL2 is capable of stimulating different populations of T cells in humans to induce either T effector or T regulatory responses. This apparent "functional paradox" has confounded a clear understanding of the mechanisms behind the clinical effects that are observed during and following administration of IL2 therapy. An average complete response rate of around 7% in small and large clinical trials using IL2 for advanced renal cell carcinoma and malignant melanoma has been shown from a recent review of the literature. Conclusion: This review considers the published literature concerning the actions and emerging clinical effects of IL2 therapy...

Lymphokines, including interleukin-2, alter gonadotropin-stimulated progesterone production and proliferation of human granulosa-luteal cells in vitro

Wang, L.; Robertson, S.A.; Seamark, R.F.; Norman, R.J.
Fonte: Endocrine Society Publicador: Endocrine Society
Tipo: Artigo de Revista Científica
Publicado em //1991 EN
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The effects of human interleukin-1 (IL-1) and IL-2 on human granulosa-luteal cell progesterone production were examined with or without hCG stimulation in vitro. Human granulosa-luteal cells were recovered from follicular fluid obtained from women undergoing in vitro fertilization procedures and cultured for up to 7 days before supernatant progesterone level measurement. Lymphokine-rich conditioned medium was prepared from mitogen-stimulated human peripheral blood leukocytes (HPL-CM). The influence of HPL-CM on both granulosa-luteal cell progesterone production and cell growth was inhibitory. In contrast, supernatants of the IL-2-producing cell line MLA-144 (MLA-CM) stimulated both basal progesterone secretion and cell proliferation. Human recombinant IL-2 (from 0.1-100 IU) alone did not change progesterone levels, compared to control values, after 24 h of cell culture. However, 1, 10, and 100 IU IL-2 significantly inhibited progesterone secretion from cells stimulated by 5 IU hCG (P less than 0.01). The enhanced progesterone levels stimulated by forskolin were also significantly inhibited by 10 IU IL-2 (P = 0.01). This effect was not mediated through decreased cAMP, since the forskolin-enhanced cAMP level was not influenced by IL-2...

Interleukin-2 and its receptor complex (alpha, beta and gamma chains) in in situ and infiltrative human breast cancer: an immunohistochemical comparative study

García-Tuñón Llanio, Ignacio; Ricote Belinchón, Mónica; Ruiz, Antonio; Fraile Láiz, Benito; Paniagua Gómez Alvarez, Ricardo; Royuela García, María del Mar
Fonte: BioMed Central Publicador: BioMed Central
Tipo: Artigo de Revista Científica Formato: application/pdf
ENG
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The presence and distribution of interleukin-2 (IL-2) and its receptor complex (Ralpha, Rbeta, Rgamma) were studied in 52 women who were clinically and histopathologically diagnosed with breast tumours ( 17 in situ and 35 infiltrating), and in 13 women with benign fibrocystic lesions in the breast. Methods. Immunohistochemistry with antibodies against IL-2, IL-2Ralpha, IL-2Rbeta and IL-2Rgamma was used. A comparative semiquantitative immunohistochemical study between the three breast groups ( fibrocystic lesions, in situ tumours and infiltrating tumours) was performed. Results. IL-2 and its three receptor chains were immunodetected in the cytoplasm of epithelial cells. The three receptor chains were also detected on the cell surface. In fibrocystic lesions, immunoreactions to IL-2 (38.5% of cases), IL-2Ralpha (53.8%) and IL-2Rbeta (30.8%) were very weak, whereas immunoreaction to IL-2Rgamma (46.1%) was somewhat more intense. In in situ tumours, the percentages of cases that immunostained positively for IL-2 and its three receptor chains were similar to those observed in fibrocystic lesions, but immunostainings of the four antibodies were more intense. In infiltrative tumours, the percentages of positively stained cases and also immunostaining intensities were approximately twice that found for in situ tumours. Within infiltrating tumours...

Defective production of interleukin 2 in patients with Chagas' disease: purified IL-2 augments in vitro response in patients with chagasic cardiomyopathy

Briceno,Luis; Mosca,Walter
Fonte: Instituto Oswaldo Cruz, Ministério da Saúde Publicador: Instituto Oswaldo Cruz, Ministério da Saúde
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/10/1996 EN
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The production of interleukin 2 (IL-2) by peripheral blood mononuclear cells, from patients with different clinical forms of Chagas disease and healthy controls, was evaluated after stimulation with Trypanosoma cruzi antigen, PPD and PHA. PHA induced higher production of IL-2 in infected patients than healthy controls. No diferences were found between infected groups. With PPD the trend was similar, the only difference was that asymptomatic infected patients (INF) showed higher levels of IL-2 production than patients with cardiomyopathy (CDM). With T. cruzi antigen, most patients showed little or no IL-2 production at 24 hr, a peak at 48 hr and an abrupt fall at 72 hr. A similar pattern of IL- 2 production was observed in INF and CDM. To evaluate the physiologic relevance of the deficit in IL-2 production, we studied the effect of non-mitogenic concentratios of IL-2 in the proliferative response to specific antigens. The addition of IL-2 only enhanced the proliferative response of CDM patients. These observations suggest that patients suffering Chagas' disease, particularly CDM, have a significant reduction in the capacity to produce IL-2. These findings could be of importance in the pathogenesis of Chagas' disease.

Concentrações de interleucina-2 na secreção nasofaríngea de crianças com bronquiolite viral aguda pelo vírus respiratório sincicial; Concentrations of interleukin-2 in the nasopharyngeal secretion of children with acute respiratory syncytial virus bronchiolitis

Giugno, Katia Maria; Machado, Denise Cantarelli; Amantea, Sergio Luis; Menna Barreto, Sérgio Saldanha
Fonte: Universidade Federal do Rio Grande do Sul Publicador: Universidade Federal do Rio Grande do Sul
Tipo: Artigo de Revista Científica Formato: application/pdf
POR
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Objetivo: Avaliar as concentrações de interleucina-2 (IL-2) na secreção nasofaríngea de crianças (0-24 meses) acometidas de bronquiolite viral aguda pelo vírus respiratório sincicial nas primeiras 12 horas de hospitalização e correlacionar os níveis encontrados com a gravidade da doença. Métodos: Estudo prospectivo com amostragem seqüencial realizado no período de junho a agosto de 1999. Foram incluídos 62 pacientes previamente hígidos, internados com diagnóstico de bronquiolite viral aguda caracterizado por pródromos recentes de coriza e/ou obstrução nasal que evoluíram com pelo menos dois dos seguintes sinais: disfunção respiratória, taquipnéia, sibilos ou crepitações. Todos os pacientes tiveram a presença de vírus respiratório sincicial detectada no aspirado nasofaríngeo. As amostras de secreção nasofaríngea foram obtidas nas primeiras 12 horas de hospitalização. As dosagens de IL- 2 foram realizadas por ensaio imunoenzimático. A gravidade da doença foi avaliada por: medida da saturação de oxigênio da hemoglobina por oximetria de pulso, sistema de escore clínico modificado, tempo de uso de oxigênio, tempo de hospitalização e necessidade de ventilação mecânica, sendo estas variáveis comparadas em relação às medianas de IL-2 através dos testes de Spearman e Kruskal-Wallis e...

Control of interleukin-2 gene transcription: a paradigm for inducible, tissue-specific gene expression

Bunting, Karen; Wang, Jun; Shannon, M Frances
Fonte: Academic Press Publicador: Academic Press
Tipo: Artigo de Revista Científica
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Interleukin-2 (IL-2) is a key cytokine that controls immune cell function, in particular the adaptive arm of the immune system, through its ability to control the clonal expansion and homeostasis of peripheral T cells. IL-2 is produced almost exclusively

Protooncogene-encoded protein kinases in interleukin-2 signal transduction

Reed, John C.; Torigoe, Toshihiko; Turner, Bruce C.; Mérida, Isabel; Gaulton, Glen; Saragovi, H. Uri; Rapp, Ulf R.; Taichman, Russell
Fonte: Elsevier Publicador: Elsevier
Tipo: Artículo
ENG
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Protooncogenes are the normal forms of cellular genes that when altered in their expression or coding sequences can contribute to neoplastic transformation. As these genes often are important for normal cellular growth control, we explored the possibility that protein kinases encoded by particular protooncogenes could participate in signal transduction pathways regulated by the T cell growth factor, interleukin-2 (IL-2). In this review we summarize our findings to date regarding Raf-1, a serine/threonine-specific kinase that becomes phosphorylated on tyrosine residues and enzymatically activated in response to IL-2 stimulation. In addition, we describe our investigations of Lck and Lyn, two closely related protein tyrosine kinases of the src gene family that physically associate with the IL-2 receptor complex and whose activities are regulated by IL-2 in at least some T cells and B cells, respectively.; This work was supported in part by NIH Grant CA-54957.; Peer reviewed

Dendritic cells infected with a vaccinia virus interleukin-2 vector secrete high levels of IL-2 and can become efficient antigen presenting cells that secrete high levels of the immunostimulatory cytokine IL-12

Mukherjee, Sutapa; Upham, John; Ramshaw, Ian; Bundell, Christine; van Bruggen, Ivonne; Robinson, Bruce; Nelson, Delia
Fonte: Nature Publishing Group Publicador: Nature Publishing Group
Tipo: Artigo de Revista Científica
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Dendritic cell (DC) therapies using DC presenting tumor antigen/s can induce CD8+ CTL that mediate tumor eradication, nonetheless many patients remain unresponsive. Thus, cytokine gene vectors applied to DC may amplify these responses. Herein, we examined the responses that monocyte-derived DC (at different maturational stages) make when infected with a vaccinia virus-interleukin-2 (VV-IL-2) vector in vitro. VV-IL-2-infected DC secreted significant levels of bioactive IL-2 and maintained their antigen presentation function. However, we show that DC are exquisitely sensitive to their local antigenic microenvironment, and that responses generated by one antigen can be altered by another. VV-IL-2 infection of immature DC led to DC activation (upregulation of CD80, CD86 and class II surface molecules) when the virus was propagated through xenogeneic, but not syngeneic, mammalian cells; these DC secreted IL-10 and tumor necrosis factor-α (TNF-α), but not IL-12. In contrast, after VV-IL-2 infection (regardless of their mammalian cellular context), IFNγ/LPS-matured DC inevitably downregulated their antigen presenting machinery. In conclusion, immunostimulatory DC can be generated by VV-IL-2, but this depends upon (i) infecting immature DC only...

The complete cDNA Sequences of IL-2, IL-4, IL-6 and IL-10 from the European rabbit (oryctolagus cuniculus)

Perkins, Harvey; van Leeuwen, Barbara; Hardy, Chris M; Kerr, P J
Fonte: Academic Press Publicador: Academic Press
Tipo: Artigo de Revista Científica
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The cDNAs for four rabbit cytokine genes [interleukin 2 (IL-2), IL-4, IL-6 and IL-10] have been cloned from primary lymphocytes by polymerase chain reaction (PCR) methods. IL-2 and IL-10 are both highly conserved between rabbit and other species, IL-4 and IL-6 are less strongly conserved, at both nucleotide and amino acid levels, and exhibit structural differences. An extension of the coding region of rabbit IL-6 relative to all other reported IL-6 genes results from a mutation in the usual stop codon which allows translation to continue for a further 27 amino acids. Analysis of IL-6 from four other lagomorph species suggests that this mutation is specific to the European rabbit. Sequence and structural differences of IL-4 and IL-6, while presumably not altering function, may render them highly species-specific. Several alternatively spliced variants of IL-2 and IL-4 are also reported. (C) 2000 Academic Press.

Histone Dynamics on the Interleukin-2 Gene in Response to T-Cell Activation

Chen, Xin; Wang, Jun; Woltring, Donna; Gerondakis, Steve; Shannon, M Frances
Fonte: American Society for Microbiology Publicador: American Society for Microbiology
Tipo: Artigo de Revista Científica
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Several models have been proposed for the mechanism of chromatin remodelling across the promoters of inducible genes in mammalian cells. The most commonly held model is one of cooccupation where histone proteins are modified by acetylation or phosphorylation and nucleosomes are remodelled, allowing the assembly of transcription factor complexes. Using chromatin immunoprecipitation, we observed an apparent decrease of histone acetylation and phosphorylation signals at the proximal promoter region of the inducible interleukin-2 and granulocyte-macrophage colony-stimulating factor genes in response to T-cell activation. We showed that this apparent decrease was due to a loss of histone H3 and H4 proteins corresponding to a decrease in nucleosome occupation of the promoter. This histone loss is reversible; it is dependent on the continual presence of appropriate activating signals and transcription factors and is not dependent on the acetylation status of the histone proteins. These data show for the first time that histone proteins are lost from a mammalian promoter upon activation of transcription and support a model of activation-dependent disassembly and reassembly of nucleosomes.

Interleukin-2 Receptor Serum Concentrations in Normal Pregnancy and Preeclampsia

Romero-Adrián,Tania; Ruiz,Ana; Molina-Vílchez,Rafael; Estévez,Jesús; Atencio,Ricardo
Fonte: Universidad del Zulia Publicador: Universidad del Zulia
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/04/2002 EN
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The purpose of this research was to assess interleukin-2 receptor serum levels in normal pregnancy and pre-eclampsia. Sera from 90 healthy pregnant women (30 for each trimester), 30 with pre-eclampsia and a group of 30 healthy non-pregnant were analyzed. Soluble interleukin-2 receptor was measured by specific double antibody enzymatic immunoassay (ELISA). Results were: 267.5 ± 12.3 (mean ± s.e.m) pg/mL in the uncomplicated first trimestre sample, 300.9 ± 14.5 pg/mL in the second trimester and 248.8 ± 12.5 pg/mL in the third. The non-pregnant control group had 443.7 ± 39.6 pg/mL, significantly different from normal pregnancy in all trimesters (p < 0.001). The concentration in pre-eclamptic patients was 382.2 ± 24.2 pg/mL, with p < 0.01 with regard to the normal third trimester group. The conclusion is that interleukin-2 receptor serum levels diminish in normal pregnancy and rise in preeclampsia. The first finding seems to be a protective mechanism to the fetal allograft. The latter, point to increased cellular activity.