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Construção e avaliação da ação de plasmídio contendo gene suicida timidina quinase e gene imunomodulador da interleucina 12 otimizada, visando terapia gênica para carcinoma medular de tireóide; Construction and evaluation of plasmid expressing thymidine kinase suicide gene and immunomodulatory evolved interleukin-12 gene for medullary thyroid carcinoma gene therapy

Seidenberger, Katia
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 14/09/2007 Português
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Os tratamentos convencionais para carcinoma medular de tireóide (CMT) metastático são insatisfatórios. Tanto a quimioterapia quanto a radioterapia são pouco eficazes para a doença avançada. Portanto, a terapia gênica é uma promissora opção. Trabalhos de construção de vetores plasmidiais ou adenovirais específicos para cultura de células de carcinoma medular de tireóide e/ou animais têm demonstrado resultados encorajadores, conseguindo significativa redução do tumor. O objetivo deste trabalho foi construir e avaliar a eficácia do plasmídio pTCPtkevIL-12 contendo o gene da timidina quinase (HSV-tk) e da interleucina 12 otimizada/evolved (evIL-12), ambos sob controle do promotor da calcitonina modificado (TCP), visando terapia gênica do CMT. A associação entre um gene ?suicida? (TK) e um gene imunomodulador (IL12) é sabidamente sinérgica, o que motivou o emprego destes dois genes no vetor terapêutico. Por melhoramento genético, obteve-se recentemente a IL-12 otimizada/evolved, com elevada capacidade em induzir resposta imune. O promotor TCP é mais forte e mais específico que o promotor de calcitonina natural , e já foi usado em diversos trabalhos em CMT. Para determinar a atividade biológica das interleucinas 12 (evIL-12 e mIL-12)...

Níveis de interleucina-6 e fator de necrose tumoral-alfa no liquor de recém-nascidos a termo com encefalopatia hipóxico-isquêmica; Levels of interleukin-6 and tumor necrosis factor-alpha in the cerebrospinal fluid of full-term newborns with hypoxic-ischemic encephalopathy

Silveira, Rita de Cássia dos Santos; Procianoy, Renato Soibelmann
Fonte: Universidade Federal do Rio Grande do Sul Publicador: Universidade Federal do Rio Grande do Sul
Tipo: Artigo de Revista Científica Formato: application/pdf
Português
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Objetivo: avaliar os níveis liquóricos de IL-6 e TNF-a em recém-nascidos a termo com encefalopatia hipóxico-isquêmica (EHI), comparando-os com os de recém-nascidos controles. Metodologia: estudo caso-controle realizado no período de julho de 1999 a outubro de 2001, incluindo dois grupos de recémnascidos a termo: controle, com 20 recém-nascidos sem sepse e/ou meningite e com escore de Apgar > 9 no primeiro e quinto minutos de vida; e casos, com 15 recém-nascidos asfixiados, caracterizados pelo escore de Apgar < 4 e < 6 no primeiro e quinto minutos de vida, respectivamente, pH umbilical < 7,20 e/ou lactato arterial umbilical > 3,0 mmol/l e necessidade de ventilação com pressão positiva pelo menos durante 2 minutos após o nascimento. Foram coletadas amostras de liquor nas primeiras 48 horas de vida, para determinação dos níveis de IL-6 e TNF-a pelo método de enzimoimunoensaio. Resultados: os grupos não diferiram quanto ao peso de nascimento, idade gestacional, classificação quanto ao peso e idade gestacional, tipo de parto e tempo médio de obtenção do liquor; seus exames foram obtidos em média com 17 horas de vida. Nos recémnascidos asfixiados, as medianas dos níveis liquóricos foram: 157,5 pg/ml para IL-6 e 14...

The role of interleukin-10 in the differential expression of interleukin-12p70 and its beta 2 receptor on patients with active or treated paracoccidioidomycosis and healthy infected subjects

Romano, C. C.; Mendes Giannini, Maria José Soares; Duarte, A. J. S.; Benard, G.
Fonte: Elsevier B.V. Publicador: Elsevier B.V.
Tipo: Artigo de Revista Científica Formato: 86-94
Português
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Paracoccidioidomycosis patients present an antigen-specific Th1 immunosuppression. To better understand this phenomenon, we evaluated the interleukin (IL)-12 pathway by measuring IL-12p70 production and CD3(+) T cell expression of the IL-12 receptor (IL-12R)beta1/beta2 chains, induced with the main fungus antigen (gp43) and a control antigen, from Candida albicans (CMA). We showed that gp43-induced IL-12p70 production and IL-12Rbeta2 expression were significantly decreased in acute and chronic patients as compared to healthy subjects cured from PCM or healthy infected subjects from endemic areas. Interestingly, the healthy infected Subjects had higher gp43-induced IL12p70 production and beta2 expression than the cured subjects. The addition of a neutralizing anti-IL-10 antibody to the cultures increased IL12p70 levels and beta2 expression in acute and chronic patients to levels observed in Cured subjects. Conversely, addition of the cytokine IL-10 strongly inhibited both parameters in the latter group. In conclusion, we have shown that paracoccidioidomycosis-related Th1 immunosuppression is associated with down-modulation of the IL-12 pathway, that IL-10 may participate in this process, and that patients cured from paracoccidioidomycosis may not fully recover their immune responsiveness. (C) 2004 Elsevier B.V. All rights reserved.

An immunohistochemical study of interleukin-8 (IL-8) in breast cancer

Pires de Campos Zuccari, Debora Aparecida; Leonel, Camila; Castro, Rodrigo; Gelaleti, Gabriela Bottaro; Jardim, Bruna Victorasso; Moscheta, Marina Gobbe; Regiani, Vitor Rafael; Ferreira, Livia Carvalho; Lopes, Juliana Ramos; Neto, Dalisio de Santi; Esteve
Fonte: Elsevier Gmbh, Urban & Fischer Verlag Publicador: Elsevier Gmbh, Urban & Fischer Verlag
Tipo: Artigo de Revista Científica Formato: 571-576
Português
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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP); The use of prognostic markers for breast cancer is important for routine diagnosis and research. Interleukin-8 is a chemotactic cytokine produced by several cell types in response to inflammation, however, its expression, regulation and function are poorly understood. Recent studies have associated angiogenesis and inflammatory processes with tumor malignancy. The present study investigated the correlation between interleukin-8 expression and breast cancer prognosis. Interleukin-8 expression was assessed in 72 women with mammary neoplasia by immunohistochemistry and the results were statistically correlated with clinical-pathological findings. There was an inverse correlation between interleukin-8 expression and metastasis (p = 0.03) and/or local recurrence (p = 0.02). In the patient group that received post-surgery chemotherapy and radiotherapy, a lower interleukin-8 expression was found in those women that showed local recurrence (p = 0.01). Multivariate logistic regression showed estrogen receptor negativity, progesterone positivity and metastasis with increased risk of death (p < 0.05). The data reflect the complexity of the role of interleukin-8 in tumor microenvironment and support its classification as a possible prognostic marker...

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
Português
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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.

Plasma levels of interleukin-10 and nitric oxide in response to two different desflurane anesthesia flow rates

Kalayci,Dilek; Dikmen,Bayazit; Kaçmaz,Murat; Taspinar,Vildan; Örnek,Dilsen; Turan,Özlem
Fonte: Sociedade Brasileira de Anestesiologia Publicador: Sociedade Brasileira de Anestesiologia
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/08/2014 Português
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OBJECTIVE: This study investigated interleukin-10 and nitric oxide plasma levels following surgery to determine whether there is a correlation between these two variables and if different desflurane anesthesia flow rates influence nitric oxide and interleukin-10 concentrations in circulation. MATERIALS AND METHODS: Forty patients between 18 and 70 years and ASA I-II physical status who were scheduled to undergo thyroidectomy were enrolled in the study. INTERVENTIONS: Patients were allocated into two groups to receive two different desflurane anesthesia flow rates: high flow (Group HF) and low flow (Group LF). MEASUREMENTS: Blood samples were drawn at the beginning (t 0) and end (t 1) of the operation and after 24 h (t 2). Plasma interleukin-10 and nitric oxide levels were measured using an enzyme-linked-immunosorbent assay and a Griess reagents kit, respectively. Hemodynamic and respiratory parameters were assessed. RESULTS: There was no statistically significant difference between the two groups with regard to interleukin-10 levels at the times of measurement. Interleukin-10 levels were increased equally in both groups at times t 1 and t 2 compared with preoperative concentrations. For both groups, nitric oxide circulating concentrations were significantly reduced at times t 1 and t 2 compared with preoperative concentrations. However...

Staphylococcus aureus regulates secretion of interleukin-6 and monocyte chemoattractant protein-1 through activation of nuclear factor kappaB signaling pathway in human osteoblasts

Ning,Rende; Zhang,Xianlong; Guo,Xiaokui; Li,Qingtian
Fonte: Brazilian Society of Infectious Diseases Publicador: Brazilian Society of Infectious Diseases
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/06/2011 Português
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OBJECTIVE: Activation of nuclear factor kappaB by diverse bacteria regulates the secretion of chemokines and cytokines. Staphylococcus aureus (S. aureus)-infected osteoblasts can significantly increase the secretion of interleukin-6 and monocyte chemoattractant protein-1. The aim of this study was to investigate whether S. aureus can activate nuclear factor kappaB in human osteoblasts, and whether the activation of nuclear factor kappaB by S. aureus regulates the secretion of interleukin-6 and monocyte chemoattractant protein-1. METHODS: Immunoblot and electrophoretic mobility shift assay were used to detect the degradation of IκBa and activation of nuclear factor kappaB in human osteoblasts in response to S. aureus, respectively. Enzyme-linked immunosorbent assay was used to measure the secretion of interleukin-6 and monocyte chemoattractant protein-1 in the supernatants. Lastly, carbobenzoxyl-l-leucinyl-l-leucinyl-l-leucinal, an inhibitor of the nuclear factor kappaB, was used to determine if activation of nuclear factor kappaB by S. aureus in human osteoblasts regulates the secretions of interleukin-6 and monocyte chemoattractant protein-1. RESULTS: Our results for the first time demonstrated that S. aureus can induce the degradation of IκBa and activation of nuclear factor kappaB in human osteoblasts in a time and dose-dependent manner. In addition...

A randomized trial of supplementation with docosahexaenoic acid-rich tuna oil and its effects on the human milk cytokines interleukin 1beta, interleukin 6, and tumor necrosis factor alpha

Hawkes, J.; Bryan, D.L.; Makrides, M.; Neumann, M.; Gibson, R.
Fonte: Amer Soc Clinical Nutrition Publicador: Amer Soc Clinical Nutrition
Tipo: Artigo de Revista Científica
Publicado em //2002 Português
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Background: Increased consumption of n-3 long-chain polyunsaturated fatty acids (PUFAs) has been recommended during pregnancy and lactation. The production of proinflammatory cytokines by human peripheral blood mononuclear cells (PBMCs) can be modified by dietary n-3 PUFAs. Objective: We sought to determine whether dietary supplementation of lactating women with docosahexaenoic acid (DHA) can modulate the concentration of cytokines in the aqueous phase of human milk and the production of cytokines by human milk cells (HMCs) and PBMCs. Design: In this double-blind, prospective, randomized trial, mothers of healthy full-term infants were asked to consume daily a nutritional supplement of 2000 mg oil containing either placebo (n = 40), 300 mg DHA + 70 mg eicosapentaenoic acid (EPA; n = 40), or 600 mg DHA + 140 mg EPA (n = 40). The fatty acid composition of plasma, PBMCs, milk, and HMCs from lactating mothers at 4 wk postpartum was measured by gas chromatography. The concentration of interleukin 6 and tumor necrosis factor in milk and the production of interleukin 1ß, tumor necrosis factor , and interleukin 6 by PBMCs and HMCs after stimulation with lipopolysaccharide was measured by enzyme-linked immunosorbent assay. Results: At 4 wk postpartum...

Uterine eosinophils and reproductive performance in interleukin 5-deficient mice

Robertson, S.; Mau, V.; Young, I.; Matthaei, K.
Fonte: Society for Reproduction and Fertility Publicador: Society for Reproduction and Fertility
Tipo: Artigo de Revista Científica
Publicado em //2000 Português
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Interleukin 5 is expressed in type 2 T lymphocytes and has a key role in driving the differentiation, recruitment and activation of eosinophils. Mice with a null mutation in the interleukin 5 gene (IL-5 -/- mice) have altered type 2 immune responses and severely depleted eosinophil populations. In the present study, the effect of interleukin 5 deficiency on the abundant population of eosinophils present in the female reproductive tract was investigated, and the reproductive performance in C57Bl/6 IL-5 -/- mice was measured. Endometrial eosinophils, detected on the basis of their endogenous peroxidase activity, were reduced in number by four-sevenfold during the oestrous cycle and in early pregnancy in IL-5 -/- mice. Eosinophils present in the cervix and decidual tissues at the time of parturition were similarly diminished. The temporal fluctuations in eosinophil recruitment and localization within these tissues were otherwise unchanged, indicating that interleukin 5 is not a necessary chemotactic agent in the female reproductive tract. Oestrous cycles were moderately greater in duration in IL-5 -/- mice (mean +/- SD = 5.6 +/- 1.0 days in IL-5 -/- mice versus 5.0 +/- 0.8 days in IL-5 +/+ mice), owing to an extended period in oestrus (2.7 +/- 0.9 days per cycle in IL-5 -/- mice versus 1.8 +/- 0.7 in IL-5 +/+ mice). The interval between placing females with males and the finding of copulatory plugs was reduced significantly in interleukin 5-deficient mice. Implantation rates and subsequent fetal development were comparable in IL-5 -/- and IL-5 +/+ mice...

Early expression and cellular localization of proinflammatory cytokines interleukin-1[beta], interleukin-6, and tumor necrosis factor-[alpha] in human traumatic spinal cord injury

Yang, L.; Blumbergs, P.; Jones, N.; Manavis, J.; Sarvestani, G.; Ghabriel, M.
Fonte: Lippincott Williams & Wilkins Publicador: Lippincott Williams & Wilkins
Tipo: Artigo de Revista Científica
Publicado em //2004 Português
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Study Design. Post-traumatic inflammatory response was studied in 11 human cases of acute spinal cord contusion injury. Objectives. To examine the inflammatory cellular response and the immunocytochemical expression and localization of interleukin-1[beta], internleukin-6, and tumor necrosis factor-[alpha]in human spinal cord after contusion injury. Summary of Background Data. The post-traumatic inflammatory response plays an important role in secondary injury mechanisms after spinal cord injury, and inter-leukin-1[beta], internleukin-6, and tumor necrosis factor-[alpha] are key inflammatory mediators. Methods. The study group comprised 11 patients with spinal cord contusion injury and 2 normal individuals. Histologic and immunocytochemical assessments were undertaken to evaluate the inflammatory cellular response and the immunoexpression of interleukin-1[beta], internleukin-6, and tumor necrosis factor-[alpha] in the injured human spinal cord. The cellular sources of interleukin-1[beta], internleukin-6, and tumor necrosis factor-[alpha] were elucidated by immunofluorescence double-labeled confocal imaging. Results. Increased immunoreactivity of interleukin-1[beta], internleukin-6, and tumor necrosis factor-[alpha]was detected in neurons 0.5 hour after injury...

Shiga toxin 2 and Flagellin from Shiga-toxigenic Escherichia coli superinduce interleukin-8 through synergistic effects on host stress-activated protein kinase activation

Jandhyala, D.; Rogers, T.; Kane, A.; Paton, A.; Paton, J.; Thorpe, C.
Fonte: Amer Soc Microbiology Publicador: Amer Soc Microbiology
Tipo: Artigo de Revista Científica
Publicado em //2010 Português
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Shiga toxins expressed in the intestinal lumen during infection with Shiga-toxigenic Escherichia coli must translocate across the epithelium and enter the systemic circulation to cause systemic (pathological) effects, including hemolytic uremic syndrome. The transepithelial migration of polymorphonuclear leukocytes in response to chemokine expression by intestinal epithelial cells is thought to promote uptake of Stx from the intestinal lumen by compromising the epithelial barrier. In the present study, we investigated the hypothesis that flagellin acts in conjunction with Shiga toxin to augment this chemokine expression. We investigated the relative contributions of nuclear factor B (NF-B) and mitogen-activated protein kinase (MAPK) signaling to transcription and translation of interleukin-8. Using reporter gene constructs, we showed that flagellin-mediated interleukin-8 gene transcription is heavily dependent on both NF-B and extracellular signal-regulated kinase 1 and 2 (ERK-1/2) activation. In contrast, inhibition of p38 has no detectable effect on interleukin-8 gene transcription, even though flagellin-mediated activation of host p38 is critical for maximal interleukin-8 protein expression. Inhibition of MAPK-interacting kinase 1 suggests that p38 signaling affects the posttranscriptional regulation of interleukin-8 protein expression induced by flagellin. Cotreatment with Stx2 and flagellin results in a synergistic upregulation of c-Jun N-terminal protein kinases (JNKs)...

Interleukin-10 Therapie bei Psoriasis; Interleukin-10 therapy in Psoriasis

Schmid, Hans-Peter Christian
Fonte: Universidade de Tubinga Publicador: Universidade de Tubinga
Tipo: Dissertação
Português
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Bei der vorliegenden Untersuchung handelt es sich um eine klinische Pilotstudie, welche die Wirkung von Interleukin-10 (IL-10) bei Psoriasis überprüft. Von den 10 rekrutierten Probanden wurden die ersten 5 Patienten mit 4 µg/Kg Körpergewicht IL-10 täglich behandelt, die nachfolgenden 5 Patienten erhielten die gleiche Dosis nur jeden zweiten Tag. Das IL-10 wurde über 42 Tage subkutan in einen psoriasisfreien Hautbezirk gespritzt. Anschließend wurde der Verlauf der Erkrankung in einer Nachbeobachtung für weitere 6 Wochen dokumentiert. Bedingung zur Aufnahme in die Studie war das Vorhandensein einer ausgeprägten Psoriasiserkrankung mit einer erkrankten Hautoberfläche von mindestens 10%. In den vorausgegangenen 4 Wochen vor Studieneintritt durften keine systemischen immunsuppressiven Therapien durchgeführt werden und eine antipsoriatische Lokaltherapie musste spätestens 1 Woche vor Studienbeginn abgesetzt werden. Bösartige Tumorerkrankung in der Vorgeschichte, sowie eine positive HIV-, Hepatitis-B- und C-Serologie mussten im Vorfeld ausgeschlossen werden. Probanden beider Geschlechter konnten im Alter zwischen 18 und 70 Jahren eingeschlossen werden. Der klinische Verlauf wurde mittels PASI-Score (Psoriasis Activity Severity Index)...

Einflussfaktoren auf Interleukin-8-Konzentrationen in Plasma und lysiertem Vollblut beim Neugeborenen; Influencing factors on plasma and DLWB interleukin-8-concentrations in newborns

Siedler, Diana
Fonte: Universidade de Tubinga Publicador: Universidade de Tubinga
Tipo: Dissertação
Português
Relevância na Pesquisa
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Einflussfaktoren auf Interleukin-8-Konzentrationen in Plasma und lysiertem Vollblut beim Neugeborenen D. Siedler, M. Deperschmidt#, C. Henkel#, M. Eichner*, Ch. F. Poets, Th. Orlikowsky Univ.-Kinderklinik Tübingen, Abt. Neonatologie, #Univ.-Frauenklinik Tübingen, *Institut für medizinische Biometrie Tübingen Hintergrund: Trotz wirksamer Antibiotikatherapie ist die frühe neonatale bakterielle Infektion (EOBI) mit einer hohen Morbidität und Mortalität verbunden. Deshalb ist die frühzeitige Diagnose und Behandlung wichtig, um Spätfolgen zu verhindern und eine normale Entwicklung des Kindes zu gewährleisten. IL-8 ist ein Akutphase-Zytokin, welches früh bei bakteriellen Infektionen ausgeschüttet wird. Es wird neben den spezifischen IL-8-Rezeptoren auf Granulozyten auch unspezifisch an Erythrozyten gebunden. Im Plasma gemessen ist seine Halbwertszeit kurz und beträgt ein bis drei Stunden. In lysiertem Vollblut erwies es sich als Parameter, welcher der Plasmabestimmung im Hinblick auf Sensivität, Spezifität sowie dem prädiktiven Wert bei EOBI überlegen war. Ziel: Untersuchung von Einflussgrößen prä-, peri- und postnataler Faktoren, hierbei insbesondere des Erythrozytenstatus, auf IL-8-Konzentrationen in Plasma und lysiertem Vollblut...

Serielle Lactatbestimmung als prognostischer Parameter nach Herzoperationen im Kindesalter - Vergleich mit der prognostischen Aussagekraft von Procalcitonin, Interleukin 6 und 8 in Bezug auf das postoperative Geschehen nach Herzoperationen im Kindesalter; Serial measurement of lactate as a prognostic parameter after heart surgery in children- a comparison with the prognostic meaning of procalcitonin, interleukin 6 and 8 referring to the postoperative course in infancy

Weiß, Christine
Fonte: Universidade de Tubinga Publicador: Universidade de Tubinga
Tipo: Dissertação
Português
Relevância na Pesquisa
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Lactat entsteht bei der anaeroben Glykolyse. Das postoperative Lactat ermöglicht, das Ausmaß der intraoperativen Gewebehypoxie mit eventuellen Folgeschäden abzuschätzen. Procalcitonin, ein aus 116 Aminosäuren bestehendes Protein, und die Interleukine 6 und 8, zur Gruppe der Zytokine gehörend, dienen als Inflammationsmarker. Die vorliegende Arbeit besteht aus zwei Teilen. Im ersten Teil wurde im Rahmen einer retrospektiven Studie bei 253 an der Universitäts-Kinderklinik Tübingen in der Zeit von März 1997 bis Mai 1998 am Herzen operierten Kinder die postoperativen Lactatspiegel bestimmt. Die Kinder waren zwischen einem Tag und 16,5 Jahren alt. Ein Ziel war es herauszufinden, ob das Lactat ein Parameter ist, der zur Vorhersage des postoperativen Outcomes beitragen kann. Im zweiten Teil, einer prospektiven Studie, wurden Lactatspiegel bei 51 Kindern, die in der Zeit von August 2000 bis Februar 2001 ebenfalls an der herzchirurgischen Abteilung der Universitätskinderklinik Tübingen am Herzen operiert wurden, untersucht. Diese Kinder waren zwischen 4 Tagen und 16 Jahre alt. Die Lactatverläufe wurden bis zum 6. postoperativen Tag analysiert. Zusätzlich wurde sieben Mal bis zum 6. postoperativen Tag die Bestimmung von Procalcitonin (PCT)...

Hat das vom Embryo produzierte hCG einen Einfluss auf Interleukin-11 und Interleukin-15 in dezidualisierten humanen endometrialen Stromazellen?; Does hCG, which is produced by the embryo, have an influence on interleukin-11 and interleukin-15 in decidualized human endometrial stromal cells?

Sachs-Nill, Ellen Renate
Fonte: Universidade de Tubinga Publicador: Universidade de Tubinga
Tipo: Dissertação
Português
Relevância na Pesquisa
36.47%
Ziel dieser Arbeit war es, das Verhalten von IL-11 und IL-15 während der Dezidualisierung in humanen endometrialen Stromazellen in vitro und einen möglichen Einfluss von hCG auf diese Faktoren zu untersuchen. Hierfür wurden Primärzellkulturen von endometrialen Stromazellen verwendet. Die Proben stammten aus Hysterektomien, die prämenopausale Frauen aufgrund gutartiger Erkrankungen durchführen ließen. Die Zellkulturen wurden mit 1 myM Progesteron und 30 nM 17beta-Östradiol, sowie rekombinatem hCG inkubiert. Die Messungen von IL-11 und -15 mRNA und Proteinen wurden mittels semiquantitativer RT-PCR und ELISA durchgeführt. Während bei IL-11 keine Regulation durch hCG festgestellt wurde, konnte bei IL-15 eine signifikante Inhibition durch hohe hCG-Konzentrationen gezeigt werden. Dies unterstützt Veröffentlichungen anderer Arbeitsgruppen, die IL-11 als Schlüsselfaktor in der dezidualen Umwandlung sehen, welche zum Großteil vor der hCG-Produktion eines Embryos stattfindet. Da die IL-15 Sekretion von DSC im menschlichen Uterus die uNK zur Proliferation stimuliert, kann davon ausgegangen werden, dass hCG diese Proliferation über IL-15 Inhibition verhindert, um den Embryo nicht abzustoßen. Da die Proteindaten von IL-15 im ELISA nicht gemessen werden konnten...

Simultaneous antagonism of interleukin-5, granulocyte-macrophage colony-stimulting factor, and interleukin-3 stimulation of human eosinophils by targetting the common cytokine binding site of their receptors

Sun, Q.; Jones, K.; McClure, B.; Cambareri, B.; Zacharakis, B.; Iversen, P.; Stomski, F.; Woodcock, J.; Bagley, C.; D'Andrea, R.; Lopez, A.
Fonte: AMER SOC HEMATOLOGY Publicador: AMER SOC HEMATOLOGY
Tipo: Artigo de Revista Científica
Publicado em //1999 Português
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Human interleukin-5 (IL-5), granulocyte-macrophage colony-stimulating factor (GM-CSF), and IL-3 are eosinophilopoietic cytokines implicated in allergy in general and in the inflammation of the airways specifically as seen in asthma. All 3 cytokines function through cell surface receptors that comprise a ligand-specific alpha chain and a shared subunit (beta(c)). Although binding of IL-5, GM-CSF, and IL-3 to their respective receptor alpha chains is the first step in receptor activation, it is the recruitment of beta(c) that allows high-affinity binding and signal transduction to proceed. Thus, beta(c) is a valid yet untested target for antiasthma drugs with the added advantage of potentially allowing antagonism of all 3 eosinophil-acting cytokines with a single compound. We show here the first development of such an agent in the form of a monoclonal antibody (MoAb), BION-1, raised against the isolated membrane proximal domain of beta(c). BION-1 blocked eosinophil production, survival, and activation stimulated by IL-5 as well as by GM-CSF and IL-3. Studies of the mechanism of this antagonism showed that BION-1 prevented the high-affinity binding of (125)I-IL-5, (125)I-GM-CSF, and (125)I-IL-3 to purified human eosinophils and that it bound to the major cytokine binding site of beta(c). Interestingly...

The solution structure of the cytokine-binding domain of the common -chain of the receptors for granulocyte-macrophage colony-stimulating factor, interleukin-3 and interleukin-5

Mulhern, T.; Lopez, A.; D'Andrea, R.; Gaunt, C.; Vandeleur, L.; Vadas, M.; Booker, G.; Bagley, C.
Fonte: Academic Press Ltd Publicador: Academic Press Ltd
Tipo: Artigo de Revista Científica
Publicado em //2000 Português
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The haemopoietic cytokines, granulocyte-macrophage colony-stimulating factor, interleukin-3 and interleukin-5 bind to cell-surface receptors comprising ligand-specific alpha-chains and a shared beta-chain. The beta-chain is the critical signalling subunit of the receptor and its fourth domain not only plays a critical role in interactions with ligands, hence in receptor activation, but also contains residues whose mutation can lead to ligand-independent activation of the receptor. We have determined the NMR solution structure of the isolated human fourth domain of the beta-chain. The protein has a fibronectin type III fold with a well-defined hydrophobic core and is stabilised by an extensive network of pi-cation interactions involving Trp and Arg side-chains, including two Trp residues outside the highly conserved Trp-Ser-Xaa-Trp-Ser motif (where Xaa is any amino acid) that is found in many cytokine receptors. Most of the residues implicated in factor-independent mutants localise to the rigid core of the domain or the pi-cation stack. The loops between the B and C, and the F and G strands, that contain residues important for interactions with cytokines, lie adjacent at the membrane-distal end of the domain, consistent with their being involved cooperatively in binding cytokines. The elucidation of the structure of the cytokine-binding domain of the beta-chain provides insight into the cytokine-dependent and factor-independent activation of the receptor.

Interleukin-10 but not interleukin-18 may be associated with the immune response against well-differentiated thyroid cancer

Cunha,Lucas Leite; Tincani,Alfio Jose; Assumpção,Ligia Vera Montalli da; Soares,Fernando Augusto; Vassallo,José; Ward,Laura Sterian
Fonte: Faculdade de Medicina / USP Publicador: Faculdade de Medicina / USP
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/01/2011 Português
Relevância na Pesquisa
36.56%
OBJECTIVES: The aim of this study was to investigate the role of the interleukin-18 +105A/C and interleukin-10 -1082A/G germline polymorphisms in the development and outcome of differentiated thyroid carcinoma associated or not with concurrent thyroiditis. METHODS: We studied 346 patients with differentiated thyroid carcinomas, comprising 292 papillary carcinomas and 54 follicular carcinomas, who were followed up for 12-298 months (mean 76.10 ± 68.23 months) according to a standard protocol. We genotyped 200 patients and 144 control individuals for the interleukin-18 +105A/C polymorphism, and we genotyped 183 patients and 137 controls for the interleukin-10 -1082A/G polymorphism. RESULTS: Interleukin-18 polymorphisms were not associated with chronic lymphocytic thyroiditis or any clinical or pathological feature of tumor aggressiveness. However, there was an association between the presence of interleukin-10 variants and chronic lymphocytic thyroiditis. Chronic lymphocytic thyroiditis was present in 21.74% of differentiated thyroid carcinoma patients, most frequently affecting women previously diagnosed with Hashimoto's thyroiditis who had received a lower 131I cumulative dose and did not present lymph node metastases. CONCLUSIONS: We conclude that the inheritance of a G allele at the interleukin-10 -1082A/G polymorphism may favor a concurrent thyroid autoimmunity in differentiated thyroid carcinoma patients...

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
Português
Relevância na Pesquisa
36.52%
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...

Interleukin-10 but not interleukin-18 may be associated with the immune response against well-differentiated thyroid cancer

Cunha, Lucas Leite; Tincani, Alfio Jose; Assumpção, Ligia Vera Montalli da; Soares, Fernando Augusto; Vassallo, José; Ward, Laura Sterian
Fonte: Universidade de São Paulo. Faculdade de Medicina Publicador: Universidade de São Paulo. Faculdade de Medicina
Tipo: info:eu-repo/semantics/article; info:eu-repo/semantics/publishedVersion; ; ; ; ; ; Formato: application/pdf
Publicado em 01/01/2011 Português
Relevância na Pesquisa
36.56%
OBJECTIVES: The aim of this study was to investigate the role of the interleukin-18 +105A/C and interleukin-10 -1082A/G germline polymorphisms in the development and outcome of differentiated thyroid carcinoma associated or not with concurrent thyroiditis. METHODS: We studied 346 patients with differentiated thyroid carcinomas, comprising 292 papillary carcinomas and 54 follicular carcinomas, who were followed up for 12-298 months (mean 76.10 ± 68.23 months) according to a standard protocol. We genotyped 200 patients and 144 control individuals for the interleukin-18 +105A/C polymorphism, and we genotyped 183 patients and 137 controls for the interleukin-10 -1082A/G polymorphism. RESULTS: Interleukin-18 polymorphisms were not associated with chronic lymphocytic thyroiditis or any clinical or pathological feature of tumor aggressiveness. However, there was an association between the presence of interleukin-10 variants and chronic lymphocytic thyroiditis. Chronic lymphocytic thyroiditis was present in 21.74% of differentiated thyroid carcinoma patients, most frequently affecting women previously diagnosed with Hashimoto's thyroiditis who had received a lower 131I cumulative dose and did not present lymph node metastases. CONCLUSIONS: We conclude that the inheritance of a G allele at the interleukin-10 -1082A/G polymorphism may favor a concurrent thyroid autoimmunity in differentiated thyroid carcinoma patients...