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Endostatin gene therapy enhances the efficacy of IL-2 in suppressing metastatic renal cell carcinoma in mice

ROCHA, Flavia Gomes de Goes; CHAVES, Karen Cristina Barbosa; CHAMMAS, Roger; PERON, Jean Pierre Schatzmann; RIZZO, Luiz Vicente; SCHOR, Nestor; BELLINI, Maria Helena
Fonte: SPRINGER Publicador: SPRINGER
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
65.94%
We investigated whether the administration of IL-2 combined with endostatin gene therapy was able to produce additive or even synergistic immunomodulatory activity in a mouse model of metastatic renal carcinoma. Renca cells were injected into the tail vein of BALB/c mice. After 24 h, the animals were randomly divided into four groups (5 mice/group). One group of mice was the control, the second group received treatment with 100,000 UI of Recombinant IL-2 (Proleukin, Chiron) twice a day, 1 day per week during 2 weeks (IL-2), the third group received treatment with a subcutaneous inoculation of 3.6 x 10(6) endostatin-producing cells, and the fourth group received both therapies (IL-2 + ES). Mice were treated for 2 weeks. In the survival studies, 10 mice/group daily, mice were monitored daily until they died. The presence of metastases led to a twofold increase in endostatin levels. Subcutaneous inoculation of NIH/3T3-LendSN cells resulted in a 2.75 and 2.78-fold increase in endostatin levels in the ES and IL-2 + ES group, respectively. At the end of the study, there was a significant decrease in lung wet weight, lung nodules area, and microvascular area (MVA) in all treated groups compared with the control group (P < 0.001). The significant difference in lung wet weight and lung nodules area between groups IL-2 and IL-2 + ES revealed a synergistic antitumor effect of the combined treatment (P < 0.05). The IL-2 + ES therapy Kaplan-Meier survival curves showed that the probability of survival was significantly higher for mice treated with the combined therapy (log-rank test...

Efeito dos ácidos graxos sobre a via de sinalização da interleucina-2 em linfócitos humanos.; Regulation of IL-2 signaling by fatty acids in human lymphocytes.

Gorjão, Renata
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 19/05/2008 Português
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55.87%
Neste estudo investigamos os efeitos dos ácidos graxos sobre a função e sinalização intracelular de linfócitos humanos. Os ácidos oléico (OA) e linoléico (LA), em baixas concentrações, estimularam a proliferação celular induzida pela IL-2 através do aumento da fosforilação da proteína PKC-Z que levou a um aumento da fosforilação de ERK 1/2. Já os ácidos palmítico (PA), esteárico (SA), DHA e EPA diminuíram a proliferação destas células e inibiram a fosforilação de JAK1 e 3, STAT5, ERK e Akt. Os resultados obtidos são sugestivos de que o efeito inibitório promovido por PA, SA, DHA e EPA sobre a proliferação de linfócitos ocorreu devido à diminuição da fosforilação de proteínas fundamentais para a proliferação celular. Por outro lado, OA e LA estimularam a proliferação de linfócitos aumentando a fosforilação de ERK 1/2 através da ativação de PKC-Z, efeito dependente da PI3K. O efeito inibitório promovido pelo DHA está associado a uma alteração na quantidade de lipid rafts na membrana plasmática nos quais o receptor de IL-2 está localizado.; The effect of fatty acids (FA) on interleukin -2 (IL-2) signaling pathway in human lymphocytes was investigated. Docosahexaenoic (DHA)...

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 Português
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55.93%
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+...

Imbalance of IL-2, IFN-gamma and IL-10 secretion in the immunosuppression associated with human paracoccidioidomycosis

Benard, G.; Romano, C. C.; Cacere, C. R.; Juvenale, M.; Mendes Giannini, Maria José Soares; Duarte, A. J. S.
Fonte: W B Saunders Co Publicador: W B Saunders Co
Tipo: Artigo de Revista Científica Formato: 248-252
Português
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65.9%
Patients with paracoccidioidomycosis (PCM) display a certain degree of immunecompromise characterized by lymphocyte hyporesponsiveness to the main Paracoccidioides brasiliensis antigen (gp43). To determine whether cytokines are involved in this state, we evaluated the secretion of IL-2, IL-10 and IFN-gamma by peripheral blood mononuclear cells (PBMC) from patients with the acute (AF) and chronic (CF) forms of PCM and from healthy, P. brasiliensis-sensitized subjects. gp43-stimulated PBMC from healthy subjects produced substantial amounts of IL-2, IFN-gamma and IL-10, whereas PBMC from AF and CF patients produced low levels of IL-2 and IFN-gamma but substantial amounts of IL-10, Phytohaemagglutinin-induced cytokine secretion was comparable among AF and CF patients and healthy subjects, suggesting integrity of non-specific cellular immune mechanisms in PCM. gp43-pulsed adherent cells, but not non-adherent cells, mere the main source of IL-10, Moreover, IL-2 and IFN-gamma secretion correlated inversely with the amount of specific antibodies produced by patients and healthy subjects. Our results suggest that the imbalance in cytokine production of patients with PCM plays a role in the gp43-hyporesponsiveness and the marked (non-protective) antibody production of these patients. (C) 2001 Academic Press.

IL-2 AND IFN-g, BUT NOT IL-4 SECRETION BY PERIPHERAL BLOOD MONONUCLEAR CELLS (PBMC) ARE RELATED TO CD4+ T CELLS AND CLINICAL STATUS IN BRAZILIAN HIV-1-INFECTED SUBJECTS

HONG,Marisa A.; WAKIM,Valéria L.; SALOMÃO,Simone J.; CAMARGO,Luizete S.; CASSEB,Jorge; DUARTE,Alberto J.S.
Fonte: Instituto de Medicina Tropical Publicador: Instituto de Medicina Tropical
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/11/1998 Português
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65.92%
It has been reported that production of IL-2 and IFN-g, known as T-helper type 1 cytokines, by peripheral mononuclear cells (PBMC) decreases with progression of HIV infection. In contrast, IL-4 and IL-10 production, Th2 cytokine profile, increases with HIV disease progression. PBMC were evaluated from 55 HIV-infected subjects from Divisão de Imunologia, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, to "in vitro" cytokines production after 24 hours of stimulation with PHA. Low levels of IL-4 production in both HIV- infected patients and normal subjects, were detected. The patients with CD4+ T cell counts <200 showed a significant decrease of IL-2 and IFN-g production compared to controls. Patients with higher counts of CD4+ T cells (either between 200-500 or >500 cells/mm3) also showed decreased production of IL-2 that was not statistically significant. There was a correlation between IL-2 and IFN-g release with CD4+ T cells counts. HIV-1-infected individuals with CD4+ T cells >500 cells/mm3 showed increased levels of IL-2 and IFN-g, than individuals with CD4+ T cells <500 cells/mm3. In conclusion...

CD28 Regulation of Interleukin-2 Production

Wang, Xia ; Miller, Jim
Fonte: Universidade de Rochester Publicador: Universidade de Rochester
Tipo: Tese de Doutorado
Português
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55.98%
Thesis (Ph.D.)--University of Rochester. School of Medicine & Dentistry. Dept. of Microbiology and Immunology, 2010.; CD28 is an important costimulatory molecule and critical for T cell activation survival, proliferation and differentiation. Previous studies have shown that CD28 regulates IL-2 production by upregulation of IL-2 transcription and stabilization of IL-2 mRNA. CD28 regulation of IL-2 transcription has been suggested to be mediated by an YMNM motif within the cytosolic tail. Upon tyrosine phosphorylation, the YMNM can recruit the SH2 domain containing protein, phosphoinositide-3-kinase, and lead to the activation of transcription factors necessary for IL-2 transcription. However, little is known about the mechanism of CD28-mediated stabilization of IL-2 mRNA. Our first observation is that the CD28 truncation, Δ179, lost its ability to stabilize IL-2 mRNA, indicating that the deleted 20 amino acid residues from the C-terminus of the cytosolic tail are necessary for CD28-mediated stabilization of IL-2 mRNA. Thus, we generated several CD28 mutations to identify the motif within the CD28 cytosolic tail that is necessary for CD28-mediated stabilization of IL-2 mRNA. We found that the prolines at positions 187 and 190 within the C-terminal proline-rich motif...

Development and Characterization of Attenuated IL-2 Fusion Proteins that can be Activated by Tumor-Expressed Proteases

Puskas, John A. ; Frelinger, John G.
Fonte: Universidade de Rochester Publicador: Universidade de Rochester
Tipo: Tese de Doutorado
Português
Relevância na Pesquisa
55.87%
Thesis (Ph.D.)--University of Rochester. School of Medicine & Dentistry. Dept. of Microbiology and Immunology, 2011.; Immune responses to tumors have been shown not only in experimental animal models but also in cancer patients. Unfortunately, such responses are often weak and ineffective and new strategies to improve responses are needed. One approach has been the use of high dose cytokine therapy delivered systemically, which has in some cases brought about complete remission of tumors. Unfortunately, toxic side effects of cytokine immunotherapy often limited its use. We set out to develop a general approach in which cytokines could be functionally attenuated until activated locally at the tumor site, alleviating the negative side effects of systemic delivery. Here we report the development and initial characterization of a novel class of fusion proteins in which human or mouse interleukin-2 (IL-2), a potent growth factor for immune cells including T and NK cells, is joined via a protease site to an IL-2 inhibitory component. The rationale is that upon cleavage by a protease that is preferentially expressed at the tumor site the cytokine is free to dissociate from the inhibitory component and becomes biologically available to immune cells. We designed and characterized several fusion proteins employing distinct approaches for inhibiting cytokine function. The initial strategy investigated an approach based on a steric hindrance. To test this approach we used the cytokine IL-2...

Differentielle Modulation dendritischer Zellen durch kommensale Bakterien in IL-2-defizienten Mäusen; Commensal bacteria differentially modulate dendritic cells in IL-2 deficient mice

Müller, Martina
Fonte: Universidade de Tubinga Publicador: Universidade de Tubinga
Tipo: Dissertação
Português
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65.95%
Im IL-2-defizienten Mausmodell entwickeln Mäuse unter SPF-Bedingungen eine ausgeprägte Kolitis, während Tiere unter keimfreien Bedingungen gesund bleiben (Contractor et al. 1998; Ehrhardt et al. 1997; Waidmann et al. 2003). Die Monokolonisierung mit E. coli führt zu einer Kolitisentwicklung, während B. vulgatus-monokolonisierte Tiere gesund bleiben. In kokolonisierten Tieren konnte B. vulgatus die durch E. coli induzierte Kolitis verhindern (Waidmann et al. 2003). Es wurde untersucht, ob die Monokolonisierung von E. coli oder B. vulgatus zu einer unterschiedlichen Modulation dendritischer Zellen in der Lamina propria (LP-DCs) hinsichtlich der Aktivierung und Maturation, der DC Anzahl, der Lokalisation und der DC Subpopulationen führt. Keimfreie und SPF kolonisierte Mäuse dienten dabei als Referenztiere. LP-DCs B. vulgatus monokolonisierter und E. coli/B. vulgatus kokolonisierter IL-2-/- Tiere zeigten einen semi-maturen Phänotyp (CD40loCD80loCD86loMHCIIhi), während die Monokolonisierung mit E. coli bereits vor Krankheitsbeginn zu aktivierten und maturierten LP-DCs (CD40hiCD80hiCD86hiMHCIIhi) führte. E. coli- und SPF-kolonisierte Tiere zeigten eine reduzierte Anzahl LP-DCs und eine erhöhte Anzahl CCR7+-DCs in den mesenterialen Lymphknoten im Vergleich zu B. vulgatus-kolonisierten und keimfreien Tieren. Hinsichtlich der Aktivierung von Lamina propria-T-Zellen polarisierten mature DCs T-Zellen in Richtung Th1...

Anti-IL-2 Treatment Impairs the Expansion of T-reg Cell Population during Acute Malaria and Enhances the Th1 Cell Response at the Chronic Disease

Zago, Claudia; Bortoluci, Karina Ramalho; Sardinha, Luiz Roberto; Pretel, Fernando Delgado; Méndez, Sheyla Inés Castillo; Rosário, Ana Paula Freitas do; Hiyane, Meire Ioshie; Muxel, Sandra Marcia; Rodriguez-Malaga, Sergio M.; Abrahamsohn, Ises de Almei
Fonte: PUBLIC LIBRARY SCIENCE; SAN FRANCISCO Publicador: PUBLIC LIBRARY SCIENCE; SAN FRANCISCO
Tipo: Artigo de Revista Científica
Português
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65.85%
Plasmodium chabaudi infection induces a rapid and intense splenic CD4(+) T cell response that contributes to both disease pathogenesis and the control of acute parasitemia. The subsequent development of clinical immunity to disease occurs concomitantly with the persistence of low levels of chronic parasitemia. The suppressive activity of regulatory T (T-reg) cells has been implicated in both development of clinical immunity and parasite persistence. To evaluate whether IL-2 is required to induce and to sustain the suppressive activity of T-reg cells in malaria, we examined in detail the effects of anti-IL-2 treatment with JES6-1 monoclonal antibody (mAb) on the splenic CD4(+) T cell response during acute and chronic P. chabaudi AS infection in C57BL/6 mice. JES6-1 treatment on days 0, 2 and 4 of infection partially inhibits the expansion of the CD4(+)CD25(+)Foxp3(+) cell population during acute malaria. Despite the concomitant secretion of IL-2 and expression of high affinity IL-2 receptor by large CD4(+) T cells, JES6-1 treatment does not impair effector CD4+ T cell activation and IFN-gamma production. However, at the chronic phase of the disease, an enhancement of cellular and humoral responses occurs in JES6-1-treated mice, with increased production of TNF-alpha and parasite-specific IgG2a antibodies. Furthermore...

O papel das células Treg e da IL-2 na resposta policlonal de células CD4+ durante a infecção pelo Plasmodium chabaudi.; The role of Treg cells and IL-2 in polyclonal CD4+ T cells response during Plasmodium chabaudi infection.

Zago, Claudia Augusta
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 18/04/2008 Português
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65.93%
Durante a ativação policlonal induzida pelo P. chabaudi a maior fonte de IL-2 são as células CD4+ ativadas, além disso, acorre a expansão de células Treg. No dia 7 após a infecção, a ausência de células Treg leva a uma exacerbação da ativação de células CD4+, além de altos níveis de anticorpos anti-P.chabaudi e auto-anticorpos. A neutralização da IL-2, com Mab anti-IL-2 JES6-1, na fase aguda da infecção leva a uma redução no número de células Treg. No dia 20 de infecção, a freqüência de células CD4+ ativadas esteve elevada e as células Treg voltaram aos níveis basais. Experimentos in vitro mostraram que a neutralização da IL-2 não altera a proliferação antígeno-específica de células CD4+ da fase aguda da infecção, porém, em tempos tardios da infecção houve um drástico aumento na freqüência de células CD4+ que proliferam em resposta a eritrócitos parasitados. Podemos concluir que a IL-2 e as células Treg são capazes de limitar a ativação policlonal induzida pelo P. chabaudi ainda que com cinéticas distintas.; Polyclonal activation during P. chabaudi infection results on a huge IL-2 production by activated CD4+ T cells, besides a considerable expansion of Treg cells. At day 7 after infection in the absence of Treg cells there is an enhanced response of activated CD4+ T cells...

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 Português
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55.91%
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.

Sustained in vivo signaling by long-lived IL-2 induces prolonged increases of regulatory T cells

Bell, Charles J. M.; Sun, Yongliang; Nowak, Urszula M.; Clark, Jan; Howlett, Sarah; Pekalski, Marcin L.; Yang, Xin; Ast, Oliver; Waldhauer, Inja; Freimoser-Grundschober, Anne; Moessner, Ekkehard; Umana, Pablo; Klein, Christian; Hosse, Ralf J.; Wicker, Lin
Fonte: Elsevier Publicador: Elsevier
Tipo: Article; published version
Português
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This is thefinal version. It was first published by Elsevier at http://www.sciencedirect.com/science/article/pii/S0896841114001462; Regulatory T cells (Tregs) expressing FOXP3 are essential for the maintenance of self-tolerance and are deficient in many common autoimmune diseases. Immune tolerance is maintained in part by IL-2 and deficiencies in the IL-2 pathway cause reduced Treg function and an increased risk of autoimmunity. Recent studies expanding Tregs in vivo with low-dose IL-2 achieved major clinical successes highlighting the potential to optimize this pleiotropic cytokine for inflammatory and autoimmune disease indications. Here we compare the clinically approved IL-2 molecule, Proleukin, with two engineered IL-2 molecules with long half-lives owing to their fusion in monovalent and bivalent stoichiometry to a non-FcR? binding human IgG1. Using nonhuman primates, we demonstrate that single ultra-low doses of IL-2 fusion proteins induce a prolonged state of in vivo activation that increases Tregs for an extended period of time similar to multiple-dose Proleukin. One of the common pleiotropic effects of high dose IL-2 treatment, eosinophilia, is eliminated at doses of the IL-2 fusion proteins that greatly expand Tregs. The long half-lives of the IL-2 fusion proteins facilitated a detailed characterization of an IL-2 dose response driving Treg expansion that correlates with increasingly sustained...

The Role of High-Mobility Group I(Y) Proteins in Expression of IL-2 and T Cell Proliferation

Himes, S Roy; Reeves, Raymond; Attema, Joanne; Nissen, Mark; Li, Yung; Shannon, M Frances
Fonte: American Association of Immunologists Publicador: American Association of Immunologists
Tipo: Artigo de Revista Científica
Português
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55.89%
The high-mobility group I(Y) (HMGI(Y)) family of proteins plays an important architectural role in chromatin and have been implicated in the control of inducible gene expression. We have previously shown that expression of HMGI antisense RNA in Jurkat T cells inhibits the activity of the IL-2 promoter. Here we have investigated the role of HMGI(Y) in controlling IL-2 promoter-reporter constructs as well as the endogenous IL-2 gene in both Jurkat T cells and human PBL. We found that the IL-2 promoter has numerous binding sites for HMGI(Y), which overlap or are adjacent to the known transcription factor binding sites. HMGI(Y) modulates binding to the IL-2 promoter of at least three transcription factor families, AP-1, NF-AT and NF-κB. By using a mutant HMGI that cannot bind to DNA but can still interact with the transcription factors, we found that DNA binding by HMGI was not essential for the promotion of transcription factor binding. However, the non-DNA binding mutant acts as a dominant negative protein in transfection assays, suggesting that the formation of functional HMGI(Y)- containing complexes requires DNA binding as well as protein:protein interactions. The alteration of HMGI(Y) levels affects IL-2 promoter activity not only in Jurkat T cells but also in PBL. Importantly...

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
Português
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65.91%
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
Português
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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.

A Novel Approach for Modifying Tumor Cell - Derived Plasma Membrane Vesicles to Contain Encapsulated IL-2 and Engrafted Cosmimulatory Molecules for Use Tumor Immunotherapy

Van Broekhoven, Christina; Altin, Joseph
Fonte: John Wiley & Sons Inc Publicador: John Wiley & Sons Inc
Tipo: Artigo de Revista Científica
Português
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65.79%
The genetic modification of tumor cells and delivery of cytokines have been proposed as useful strategies in the development of anti-tumor vaccines; however, a number of factors limit their use in clinical settings. To facilitate vaccine development, we explored the possibility of modifying plasma membrane vesicles (PMV) by using a novel chelator lipid, nitrilotriacetic acid ditetradecylamine (NTA-DTDA). Our analyses by flow cytometry show that NTA-DTDA can be incorporated into PMV prepared from murine P815 mastocytoma and that the incorporated NTA-DTDA permits anchoring or "engraftment" onto the vesicle surface of hexahistidine-tagged proteins such as recombinant forms of the costimulatory molecules B7.1 and CD40. The engrafted PMV also can incorporate and deliver the immunostimulatory cytokine Interleukin-2 (IL-2). Our results show that modified PMV derived from P815 cells bind the murine T cell clone D10 in a receptor-ligand dependent manner, inducing cell adhesion and promoting cell survival in vitro. The modified PMV can bind syngeneic T cells, stimulating T cell proliferation and cytotoxic T cell responses. Moreover, when used as vaccines in syngeneic animals, the modified vesicles induce significant protection against challenge with the native P815 tumor. The results indicate that PMV modified by engraftment of recombinant forms of B7.1 and CD40 and incorporation of IL-2 can be used to modulate immune responses...

Niveles de interleucina-2 y su receptor soluble en pacientes operados y transfundidos

González Rincón,Maczy; Ruiz Medina,Ana; Arteaga de Vizcaíno,Melvis; Díaz Araujo,Felipe; Weir Medina,Jesús
Fonte: Revista Cubana de Cirugía Publicador: Revista Cubana de Cirugía
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/06/2006 Português
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Se realizó un estudio aleatorio para determinar los niveles de interleucina-2 (IL-2) y su receptor soluble (RsIL-2) en pacientes operados y transfundidos, antes de la cirugía, en el hemoderivado y 24 h después de la transfusión y para relacionar los niveles de IL-2 y RsIL-2 con cada período. Mediante inmunoensayo enzimático se determinaron los niveles de de IL-2 y RsIL-2 en 40 pacientes operados, antes de la cirugía, en los derivados sanguíneos y 24 horas después de la transfusión. Se obtuvieron valores promedio de 3,98 U/mL; 3,18 U/mL e indetectable para IL-2 y de de 678,2; 1 402 y 90,34 pg/mL para RsIL-2, en los períodos respectivos. El declive de la función linfocitaria después de cirugía y transfusión se atribuye a cambios intrínsecos o a la redistribución de células T reactivas de la sangre hacia los tejidos, a factores séricos como prostaglandinas y corticoesteroides, inhibidores de IL-2 que, con los elevados valores de RsIL-2 hallados en la bolsa, explican los niveles indetectables de IL-2 a las 24 horas de la transfusión

Expresión de Interferón Gamma (IFN-g), fFactor de Necrosis Tumoral alfa (TNF-a) e Interleucinas 2, 4 y 6 ( IL-2, IL-4, IL-6) en Células de Neoplasias Intraepiteliales de Cuello Uterino: Reporte Preliminar

Pardo-Govea,Tatiana; Callejas,Diana; Núñez-Troconis,José; Araujo,Mary; Costa,Luciana; Pons,Héctor; Delgado,Mariela; Monsalve,Francisca
Fonte: Universidad del Zulia Publicador: Universidad del Zulia
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/03/2005 Português
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65.92%
El presente estudio fue realizado para determinar la expresión de citocinas tipo Th1: IL-2 y IFN-gamma, y Th2: IL-4 e IL-6, así como del TNF-alfa en pacientes con lesiones premalignas del cuello uterino (CU) y su relación con la infección por el Virus del Papiloma Humano (VPH). Se estudiaron 30 pacientes con lesiones pre-malignas del CU; NIC 1: 70%, NCI 2: 16,7% y NIC 3: 13,3%) y 9 controles con CU sanos. A cada paciente se le realizó una historia clínica, evaluación ginecológica que incluyó la toma de la citología cervico-vaginal (CCV) y biopsia de CU para estudio histológico e inmunológico. Se empleó la reacción en cadena de polimerasa (PCR) para el estudio del VPH. La expresión del IFN-gamma se encontró aumentada en pacientes con respecto al grupo control (5,06 ± 4,7 vs 0 media ± DS; p < 0,05). El TNF-alfase expresó discretamente elevado en los diferentes tipos de lesiones con respecto al grupo control (5,23 ± 3,63 vs 1,55 ± 2,65; p < 0,05). La IL-2 se encontró más elevada en los casos patológicos que en los controles (8,73 ± 5,23 vs 0,33 ± 1, p < 0,05). La IL-4 se expresó de manera no significativa en tejidos patológicos al compararlo con los controles (6,53 ± 5,23 vs 5,77 ± 7,32). La expresión de la IL-6 fue más elevada en las pacientes que en los controles (4...

Increased number of IL-2, IL-2 receptor and IL-10 positive cells in premalignant lesions of the cervix

Mindiola,Raimy; Callejas,Diana; Núñez-Troconis,José; Araujo,Mary; Delgado,Mariela; Mosquera,Jesús
Fonte: Universidad del Zulia Publicador: Universidad del Zulia
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/12/2008 Português
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65.96%
Previous studies have shown the involvement of the immune response in the progression of human uterine cervix cancer. The aim of this study was to determine the expression of Interleukin-2 (IL-2), IL-2 receptor (IL-2R) and Interleukin 10 (IL-10) in different grades of cervical intraepithelial neoplasias of the exocervix (CIN 1, 2 and 3), and its relationship with the serum cytokine profiles and human papilomavirus (HPV) infection status. Indirect immunofluorescence was used to study the expression of IL-2, IL-2R and IL-10 in human cervical samples from 50 patients and 9 normal controls. Serum IL-2, IL-2R and IL-10 were measured by ELISA and HPV DNA and HPV types were identified by PCR. Increased number of IL-2, IL-2R and IL-10 positive cells were observed in the cervix from patients with CIN, associated with the grades of dysplasia. A significant correlation was observed between IL-2 and IL-2R (p>0.0001), IL-2 and IL-10 (p > 0,0001), as well as IL-10 and IL-2R (p> 0.0001). Twenty percent of patients were HPV positive and 84 % of those patients were tissue cytokine positive. These results suggest that IL-2, IL-2R and IL-10 tissue expression may play a role in the development of cervical intraepithelial dysplasias.

Efecto de la Melatonina en la Proliferación Linfocitaria y la Producción de Interleucina 2 (IL-2) e Interleucina 1 Beta (IL-1b) en Esplenocitos de Ratones

Arias,Julia; Melean,Eddy; Valero,Nereida; Pons,Héctor; Chacín-Bonilla,Leonor; Larreal,Yraima; Bonilla,Ernesto
Fonte: Universidad del Zulia Publicador: Universidad del Zulia
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/03/2003 Português
Relevância na Pesquisa
65.91%
La Melatonina (MLT) influye en la modulación del sistema inmunitario. Previos estudios describen incremento de la proliferación celular con aumento o disminución de citocinas; otros autores reportan efectos inhibitorios o ningún efecto en las funciones inmunitarias. Debido a esta controversia, y con el objeto de estudiar el mecanismo mediante el cual la MLT ejerce sus acciones, se planteó examinar su efecto en la proliferación de esplenocitos múridos ante un estímulo mitogénico y cuantificar los niveles de IL-2 e IL-1b en ausencia o presencia de la Fitohemaglutinina (PHA) en sobrenadantes de cultivo de células esplénicas de ratones tratados o no con MLT. La respuesta linfoproliferativa se evaluó utilizando la incorporación de timidina marcada con tritio, en esplenocitos de ratones tratados con 500 µg de MLT/Kg de peso e in vitro con 5, 50 y 100 µg/mL de MLT. La detección de IL-2 e IL-1b se realizó con la técnica de ELISA. Se observó una elevación (p < 0,01) de la proliferación, a dosis óptima de PHA, de los esplenocitos tratados in vitro con 50 y 100 µg/mL de MLT, con respecto al grupo control. El tratamiento in vivo e in vitro con MLT incrementó los niveles de IL-2 e IL-1b en ausencia o presencia de PHA, manteniendo elevada la concentración de IL-1b hasta el noveno día de tratamiento. Estos resultados sugieren que la MLT actúa en forma directa en la proliferación linfocitaria uniéndose...
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