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Id: biblio-1090061
Autor: Hernandes, Camila; Gueuvoghlanian-Silva, Bárbara Yasmin; Monnaka, Vitor Ulisses; Ribeiro, Natalia Mazini; Pereira, Welbert de Oliveira; Podgaec, Sérgio.
Título: Regulatory T cells isolated from endometriotic peritoneal fluid express a different number of Toll-like receptors / Células T reguladoras isoladas do fluido peritoneal de mulheres com endometriose expressam um número diferente de receptores do tipo Toll
Fonte: Einstein (Säo Paulo);18:eAO5294, 2020. tab, graf.
Idioma: en.
Projeto: Fundação de Amparo à Pesquisa do Estado de São Paulo; . Fundação de Amparo à Pesquisa do Estado de São Paulo.
Resumo: ABSTRACT Objective To analyze and compare the expression of Toll-like receptors by regulatory T cells present in the peritoneal fluid of patients with and without endometriosis. Methods Regulatory T cells were isolated from peritoneal fluid of women with and without endometriosis, collected during surgery, and mRNA was extracted for analysis of Toll-like receptors expression by reverse-transcriptase polymerase chain reaction. Results Patients with endometriosis presented regulatory T cells expressing a larger number and variety of Toll-like receptors when compared to regulatory T cells from patients in the Control Group. Toll-like receptor-1 and Toll-like receptor-2 in regulatory T cells were expressed in both groups. All other expressed Toll-like receptors types were only found in regulatory T cells from the Endometriosis Group. Conclusion Patients with endometriosis had peritoneal regulatory T cells expressing various Toll-like receptors types.

RESUMO Objetivo Analisar e comparar a expressão de receptores do tipo Toll por células T reguladoras presentes no líquido peritoneal de pacientes com endometriose. Métodos Células T reguladoras foram isoladas do líquido peritoneal de mulheres com e sem endometriose, coletadas durante a cirurgia, e o RNAm foi extraído para análise da expressão de receptores do tipo Toll por reação em cadeia da polimerase com transcriptase reversa. Resultados Pacientes com endometriose apresentaram células T reguladoras expressando maior número e variedade de Toll por células quando comparadas com T reguladoras de pacientes do Grupo Controle. Receptores do tipo Toll-1 e receptores do tipo Toll-2 foram expressos em ambos os grupos. Todos os outros tipos de receptores Toll foram encontrados expressos apenas em células T reguladoras do grupo com endometriose. Conclusão Pacientes com endometriose apresentaram células T reguladoras peritoneais expressando vários tipos de receptores tipo Toll.
Descritores: Líquido Ascítico/patologia
Linfócitos T Reguladores/química
Endometriose/patologia
Endométrio/patologia
Receptores Toll-Like/análise
-Valores de Referência
Líquido Ascítico/imunologia
Índice de Massa Corporal
Estudos de Casos e Controles
Linfócitos T Reguladores/imunologia
Estatísticas não Paramétricas
Reação em Cadeia da Polimerase Via Transcriptase Reversa
Endometriose/imunologia
Endométrio/imunologia
Escala Visual Analógica
Limites: Humanos
Feminino
Adolescente
Adulto
Adulto Jovem
Responsável: BR1.1 - BIREME


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Id: biblio-1281364
Autor: Pati, Subhadip; Chowdhury, Anandi; Mukherjee, Sumon; Guin, Aharna; Mukherjee, Shravanti; Sa, Gaurisankar.
Título: Regulatory lymphocytes: the dice that resolve the tumor endgame
Fonte: Appl. cancer res;40:1-9, Oct. 19, 2020. ilus.
Idioma: en.
Resumo: A large number of cancer patients relapse after chemotherapeutic treatment. The immune system is capable of identifying and destroying cancer cells, so recent studies have highlighted the growing importance of using combinatorial chemotherapy and immunotherapy. However, many patients have innate or acquired resistance to immunotherapies. Long-term follow-up in a pooled meta-analysis exhibited long-term survival in approximately 20% of patients treated with immune checkpoint inhibitors or the adoptive transfer of chimeric T cells. It has been reported that high levels of immunoregulatory cells in cancer patients contribute to immunotherapy resistance via immunosuppression. Among the most important regulatory cell subtypes are the CD4+ T-regulatory cells (Tregs), identified by their expression of the well-characterized, lineage-specific transcription factor FOXP3. In addition to CD4+ Tregs, other regulatory cells present in the tumor microenvironment, namely CD8+ Tregs and IL10-producing B-regulatory cells (Bregs) that also modulate the immune response in solid and lymphoid tumors. These cells together have detrimental effects on tumor immune surveillance and anti-tumor immunity. Therefore, targeting these regulatory lymphocytes will be crucial in improving treatment outcomes for immunotherapy.
Descritores: Linfócitos T Reguladores
Imunoterapia
Neoplasias
-Imunossupressão
Responsável: BR30.1 - Biblioteca


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Id: biblio-974917
Autor: Wang, Beibei; Wang, Haoyu; Li, Peiquan; Wang, Liangliang; Liu, Hongli; Liu, Jingbo; Wang, Lihua.
Título: Relationships of interleukin-10 with the regulatory T cell ratio and prognosis of cervical cancer patients
Fonte: Clinics;73:e679, 2018. tab, graf.
Idioma: en.
Resumo: OBJECTIVE: This study investigated serum interleukin-10 (IL-10) levels, changes in peripheral blood CD4+CD25+ regulatory T cell (PBCDT) ratios, and the prognosis of cervical cancer (CC) patients. METHODS: Seventy patients with CC composed the observation group, and 70 healthy subjects composed the control group. The PBCDT ratios in the CC patients and healthy subjects were calculated. Serum IL-10 levels were detected with a double antibody sandwich enzyme-linked immunosorbent assay (ELISA). RESULTS: The PBCDT ratio was higher in the patients with active CC [12.16±2.41%] than in the control subjects [6.34±1.05%]. Serum IL-10 levels were higher in the patients with CC [384±106 pg/ml] than in the control subjects [104±50 pg/ml]; the differences in both PBCDT ratio and IL-10 level were statistically significant (p<0.01). Serum IL-10 levels were positively correlated with PBCDT ratios (r=0.375, p<0.05). The 5-year patient survival rate was significantly higher in the low serum IL-10 group (64.2%) than in the high serum IL-10 group (42.8%, p=0.012). CONCLUSIONS: PBCDT ratios and serum IL-10 levels are related to CC activity. These factors are reciprocally related and influence one another, and both are involved in the development and progression of CC. Low IL-10 expression is beneficial regarding the survival of patients with CC.
Descritores: Antígenos CD/sangue
Neoplasias do Colo do Útero/imunologia
Interleucina-10/sangue
Linfócitos T Reguladores/citologia
-Prognóstico
Fatores Socioeconômicos
Ensaio de Imunoadsorção Enzimática
Biomarcadores Tumorais/sangue
Estudos de Casos e Controles
Neoplasias do Colo do Útero/sangue
Neoplasias do Colo do Útero/virologia
Interleucina-10/imunologia
Infecções por Papillomavirus/complicações
Infecções por Papillomavirus/diagnóstico
Estimativa de Kaplan-Meier
Citometria de Fluxo
Estadiamento de Neoplasias
Limites: Humanos
Masculino
Feminino
Adulto
Pessoa de Meia-Idade
Idoso
Idoso de 80 Anos ou mais
Responsável: BR1.1 - BIREME


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Id: biblio-1133413
Autor: Siddiq, Muhammad; Wang, Fan; Xiao, Mi; Lin, Xiao Jie; Fatima, Nazira; Iqbal, Sara; Iqbal, Umar; Piao, Xian-Hua; Liu, Li.
Título: Inhibition of lipopolysaccharide-induced inflammation via the protective role of T regulatory cells in the fetal liver in a late-pregnancy preterm mouse model
Fonte: Clinics;75:e1665, 2020. tab, graf.
Idioma: en.
Resumo: OBJECTIVES: This study intended to explore the effect of T regulatory cells (Tregs) in the perinatal liver against LPS-induced inflammation in a preterm birth mouse model. Moreover, the role of adoptive Tregs on the inflammatory response induced by LPS was also studied. METHODS: Female BALB/C mice were injected intraperitoneally (IP) with LPS dissolved in normal saline solution at a dose of 50 µg/kg. Spleens from pregnant mice were used to obtain Tregs. The expression of Forkhead family transcription factor-3 (Foxp3), Interleukin-6 (IL-6), Toll-like receptor-4 (TLR-4), and Heme oxygenase-1 (HO-1) were assessed from fetal liver tissues by polymerase chain reaction and western blotting. RESULTS: LPS administered to mice induced an inflammatory response in the perinatal liver, and this inflammatory response was negatively regulated by Tregs in the experimental group. Maternal-fetal tolerance was maintained by Tregs. Transmission of Tregs was estimated in different experimental groups based on the mRNA expression of TLR-4, IL-6, HO-1, and Foxp3. CONCLUSIONS: After analysis of the experimental data, it was determined that Tregs exhibited regulatory potential against LPS-induced inflammatory response. Further, it was concluded that the transmission of Tregs improved the mother's immune tolerance against LPS-induced inflammation in the fetal liver.
Descritores: Lipopolissacarídeos/toxicidade
Nascimento Prematuro
-Linfócitos T Reguladores
Fatores de Transcrição Forkhead
Inflamação/induzido quimicamente
Fígado
Camundongos Endogâmicos BALB C
Limites: Animais
Feminino
Gravidez
Camundongos
Tipo de Publ: Research Support, Non-U.S. Gov't
Responsável: BR1.1 - BIREME


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Id: biblio-1041472
Autor: Fernandes, Erica de Souza; Lorena, Virgínia Maria de Barros; Sales, Iana Rafaela Fernandes; Albuquerque, Mônica Camelo Pessoa de Azevedo; Gomes, Yara de Miranda; Costa, Vlaudia Maria Assis; Souza, Valdênia Maria Oliveira de.
Título: Maternal schistosomiasis: IL-2, IL-10 and regulatory T lymphocytes to unrelated antigen in adult offspring mice
Fonte: Rev. Soc. Bras. Med. Trop;51(4):546-549, July-Aug. 2018. graf.
Idioma: en.
Resumo: Abstract INTRODUCTION: We evaluated IL-10, IL-2 and regulatory T cells (Treg), in response to ovalbumin (OA), in offspring from schistosomotic mouse mothers. METHODS: We used animals born (BIM) or suckled (SIM) from infected mothers; and mice born/suckled from infected (BSIM) or non-infected mothers (CONTROL). After OA+adjuvant immunization, spleen cells were cultured, with or without OA, and doubly marked for cytometry. RESULTS: BIM showed fewer CD4+/IL-2+ and more B220+/IL-10+ cells, whereas the SIM group showed increased Treg frequency. BSIM had fewer B220+/IL-10+ and Treg cells. CONCLUSIONS: Separately, gestation or nursing induced immunosuppressive cells in infected mothers, but improved anti-OA immunity when combined.
Descritores: Esquistossomose mansoni/imunologia
Anticorpos Anti-Helmínticos/imunologia
Interleucina-2/imunologia
Interleucina-10/imunologia
Linfócitos T Reguladores/imunologia
Animais Lactentes/imunologia
-Ovalbumina/imunologia
Citometria de Fluxo
Animais Lactentes/parasitologia
Camundongos
Limites: Animais
Feminino
Responsável: BR1.1 - BIREME


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Id: biblio-1013318
Autor: Burbano, Yulieth Cristina Bermúdez; Paz, Angie Vanessa Caicedo; Caldon, Cristhian Camilo Rivera; Constain, Juan Sebastián Rodríguez; Gonzáles, Gloria Inés Ávila; Hernández, Julio César Klínger; Marin-Agudelo, Nancy; Dueñas-Cuellar, Rosa Amalia; Castaño, Victoria Eugenia Niño.
Título: Low frequency of regulatory B-cells and increased CD4+ and CD8+ interferon-γ-producing cells in patients with tropical spastic paraparesis associated with human T-cell lymphotropic virus type
Fonte: Rev. Soc. Bras. Med. Trop;52:e20190101, 2019. tab, graf.
Idioma: en.
Resumo: Abstract INTRODUCTION: Tropical spastic paraparesis/HTLV-1 associated myelopathy (TSP/HAM) is a disease caused by human T-cell lymphotropic virus type 1 (HTLV-I) that mainly infects CD4 T cells-for example, those of the CD4+CD25hiFOXP3+ [Treg] phenotype-where it inhibits forkhead box protein P3 (FOXP3) expression and promotes interferon-γ (IFN-γ) expression. However, the role it exerts on regulatory B cells (CD19+CD24hiCD38hi; Breg) is unknown. METHODS: The frequencies of Treg and Breg cells was evaluated and the Th1 profiles were assessed in TSP/HAM patients and healthy control subjects. RESULTS: Low percentages of Breg cells and high production of IFN-γ were observed in patients compared to those in healthy control subjects. CONCLUSIONS: The low percentage of Breg cells in patients and the increase in the frequency of Th1 cells suggest an imbalance in the control of the inflammatory response that contributes to the immunopathogenesis of TSP/HAM.
Descritores: Linfócitos T CD4-Positivos/imunologia
Paraparesia Espástica Tropical/imunologia
Interferon gama/imunologia
Linfócitos T Reguladores/imunologia
Linfócitos T CD8-Positivos/imunologia
Linfócitos B Reguladores/imunologia
-Linfócitos T CD4-Positivos/virologia
Paraparesia Espástica Tropical/virologia
Linfócitos T Reguladores/virologia
Linfócitos T CD8-Positivos/virologia
Carga Viral
Linfócitos B Reguladores/virologia
Limites: Humanos
Masculino
Feminino
Adolescente
Responsável: BR1.1 - BIREME


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Id: biblio-1088601
Autor: Prado, Aline Defaveri do; Bisi, Melissa Cláudia; Piovesan, Deise Marcela; Bredemeier, Markus; Baptista, Talita Siara; Petersen, Laura; Bauer, Moises Evandro; Silveira, Inês Guimarães da; Mendonça, José Alexandre; Staub, Henrique Luiz.
Título: Ultrasound inflammatory parameters and Treg/Th17 cell profiles in established rheumatoid arthritis
Fonte: Adv Rheumatol;59:26, 2019. tab, graf.
Idioma: en.
Resumo: Abstract Background: Imbalance and disfuntion in regulatory T-cells (Tregs) and IL-17 producer lymphocytes (Th17) have been implicated in the pathogenesis of rheumatoid arthritis (RA). Gray scale synovial proliferation (GS), power Doppler signal (pD) and bone erosions seen on high resolution muskuloskeletal ultrasound (MSUS) are hallmarks of destructive articular disease. Objective: To evaluate the association of peripheral Tregs and Th17 with MSUS findings in RA. Methods: RA patients (1987 ACR criteria) treated with disease-modifying antirheumatic drugs (DMARDs) were included. Lymphocytes were isolated and immunophenotyped by flow cytometry to investigate regulatory FoxP3+ T cells and IL-17+ cells. MSUS (MyLab 60, Esaote, Genova, Italy, linear probe 6-18 MHz) was performed on hand joints, and a 10-joint US score was calculated for each patient. Results: Data on lymphocytes subsets were avaiable for 90 patients. The majority of patients were Caucasian women with a median disease duration of 6 years (interquartile range: 2-13 years). Mean DAS28 was 4.28 (SD ± 1.64) and mean HAQ score was 1.11 (SD ± 0.83). There was no significant correlation of 10-joint GS score (rS = 0.122, 95% CI: - 0.124 to 0.336, P = 0.254) and 10-joint pD score (rS = 0.056, 95% CI: - 0.180 to 0.273, P = 0.602) with the mean percentage of peripheral Treg cells. Also, 10-joint GS score (rS = 0.083, 95% CI: - 0.125 to 0.302, P = 0.438) and 10-joint pD score 10 (rS = - 0.060, 95% CI: - 0.271 to 0.150, P = 0.575); did not correlate to Th17 profile. No association of bone erosions on MSUS with Treg and Th17 profiles (P = 0.831 and P = 0.632, respectively) was observed. Conclusion: In this first study addressing MSUS features and lymphocytes subtypes in established RA, data did not support an association of circulating Tregs and Th17 lymphocytes with inflammatory and structural damage findings on MSUS.
Descritores: Artrite Reumatoide/fisiopatologia
Linfócitos T Reguladores/imunologia
Células Th17/imunologia
-Ultrassonografia/métodos
Limites: Humanos
Responsável: BR1.1 - BIREME


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Id: biblio-896334
Autor: Falcão, Patrícia Lima; Campos, Tarcisio Passos Ribeiro de.
Título: The role of regulatory T cells, interleukin-10 and in vivo scintigraphy in autoimmune and idiopathic diseases - Therapeutic perspectives and prognosis / O papel de células T regulatórias, da interleucina 10 e da cintilografica in vivo em doenças autoimunes e idiopáticas - Perspectivas terapêuticas e prognóstico
Fonte: Rev. Assoc. Med. Bras. (1992);63(12):1090-1099, Dec. 2017. graf.
Idioma: en.
Resumo: Summary Previous studies have demonstrated the expression of the CD25 marker on the surface of naturally occurring T cells (Tregs) of mice, which have a self-reactive cellular profile. Recently, expression of other markers that aid in the identification of these cells has been detected in lymphocyte subtypes of individuals suffering of autoimmune and idiopathic diseases, including: CD25, CTLA-4 (cytotoxic T-lymphocyte antigen 4), HLA-DR (human leukocyte antigen) and Interleukin 10 (IL-10), opening new perspectives for a better understanding of an association between such receptors present on the cell surface and the prognosis of autoimmune diseases. The role of these molecules has already been described in the literature for the modulation of the inflammatory response in infectious and parasitic diseases. Thus, the function, phenotype and frequency of expression of the a-chain receptor of IL-2 (CD25) and IL-10 in lymphocyte subtypes were investigated. Murine models have been used to demonstrate a possible correlation between the expression of the CD25 marker (on the surface of CD4 lymphocytes) and the control of self-tolerance mechanisms. These studies provided support for the presentation of a review of the role of cells expressing IL-2, IL-10, HLA-DR and CTLA-4 receptors in the monitoring of immunosuppression in diseases classified as autoimmune, providing perspectives for understanding peripheral regulation mechanisms and the pathophysiology of these diseases in humans. In addition, a therapeutic approach based on the manipulation of the phenotype of these cells and ways of scintigraphically monitoring the manifestations of these diseases by labeling their receptors is discussed as a perspective. In this paper, we have included the description of experiments in ex vivo regulation of IL-10 and synthesis of thio-sugars and poly-sugars to produce radiopharmaceuticals for monitoring inflammation. These experiments may yield benefits for the treatment and prognosis of autoimmune diseases.

Resumo Estudos anteriores já haviam demonstrado a expressão do marcador CD25 na superfície de células T de ocorrência natural (Tregs) de camundongos, que apresentam perfil celular autorreativo. Recentemente, foi detectada, em subtipos de linfócitos de indivíduos acometidos por doenças autoimunes e de causa idiopática, a expressão de outros marcadores, que auxiliam na identificação dessas células, entre os quais: CD25, CTLA-4 (cytotoxic T-lymphocyte antigen 4), HLA-DR (human leucocyte antigen) e Interleucina 10 (IL-10), abrindo novas perspectivas para a melhor compreensão de uma associação entre esses receptores presentes na superfície celular e o prognóstico de doenças autoimunes. O papel dessas moléculas já havia sido descrito na literatura na modulação da resposta inflamatória em doenças infectoparasitárias. Dessa forma, foram investigados a função, o fenótipo e a frequência de expressão, do receptor de cadeia a da IL-2 (CD25) e de IL-10 em subtipos de linfócitos. O modelo murino tem sido utilizado para demonstrar uma possível correlação entre a expressão do marcador CD25 (na superfície de linfócitos CD4) e o controle dos mecanismos de autotolerância. Essas pesquisas forneceram suporte para apresentação de uma revisão sobre o papel das células que expressam os receptores de IL-2, IL-10, HLA-DR e CTLA-4 no monitoramento da imunossupressão, em doenças de classificação autoimune, abrindo perspectivas para o entendimento dos mecanismos de regulação periférica e sobre a fisiopatologia dessas doenças no ser humano. Além disso, é discutida como perspectiva uma abordagem terapêutica fundamentada na manipulação do fenótipo dessas células, bem como de modos de monitoramento cintilográfico das manifestações dessas doenças, por meio da marcação de seus receptores. Nestes, foram incluídas descrições das experiências em regulação ex-vivo de IL-10; de síntese de tioaçúcares e de poliaçúcares para produção de radiofármacos para monitoramento de inflamações. Essas experiências podem trazer benefícios na terapia e no prognóstico de doenças autoimunes.
Descritores: Doenças Autoimunes/diagnóstico por imagem
Autoimunidade/fisiologia
Interleucina-10/fisiologia
Linfócitos T Reguladores/fisiologia
-Prognóstico
Doenças Autoimunes/imunologia
Doenças Autoimunes/terapia
Antígenos HLA-DR
Cintilografia
Antígenos CD4/imunologia
Interleucina-10/imunologia
Modelos Animais
Subunidade alfa de Receptor de Interleucina-2/imunologia
Antígeno CTLA-4
Tolerância Imunológica
Camundongos
Limites: Humanos
Animais
Tipo de Publ: Revisão
Responsável: BR1.1 - BIREME


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Id: biblio-1178140
Autor: Leite, Caio Abner Vitorino Gonçalves.
Título: Papel da sepse na iniciação e promoção de câncer colorretal associado à colite / Role of sepsis in initiation and promotion of colitis-associated colorectal cancer.
Fonte: São Paulo; s.n; 2016. 140 p. ilust, tabelas.
Idioma: pt.
Tese: Apresentada a Fundação Antônio Prudente para obtenção do grau de Doutor.
Resumo: Introdução: O câncer colorretal (CCR) é a terceira neoplasia mais diagnosticada no mundo. A doença inflamatória intestinal é uma importante causa de CCR com patogênese atrelada à inflamação crônica. A sepse é uma doença grave que modifica a resposta imune do hospedeiro. Objetivou-se estudar se animais sobreviventes à sepse apresentam alteração na iniciação tumoral e crescimento tumoral do CCR. Material e métodos: Camundongos C57Bl6 machos foram submetidos ao modelo de ligadura e punção do ceco (CLP), e após 15 dias, os sobreviventes e um grupo controle receberam azoximetano (AOM, 10 mg/kg, i.p.) e 3 ciclos de 5 dias de dextran sulfato de sódio (DSS 2%, ad libitum) nos dias 20-25, 40-45, 60-65 pós-CLP. Foi avaliada a colite e o desenvolvimento de tumores por colonoscopia. Foram quantificadas citocinas nos dias 0 12, 52 e 65 e de células T reguladoras (Treg) nos dias 12 e 65. Dois grupos de animais C57 receberam ciclofosfamida (CYP) (100 mg/kg, i.p.) e dois grupos de animais com expressão do receptor de toxina diftérica (DTX) sob regulação do gene Foxp3 receberam DTX (0,5 mg/animal, i.p.) antes do protocolo AOM/DSS. Outro grupo de animais, foi submetido posteriormente à CLP após AOM/DSS, bem como um grupo de animais foi injetado células de CCR murino (MC38luc) 105 células no subcutâneo e outro grupo, 106 células no baço no 15 dias pós-CLP. Resultados: Animais sobreviventes à sepse apresentaram redução da colite, além de menor incidência, número de tumores e carga tumoral que animais controle. Os animais pós-sepse tiveram menor produção de IFN-γ nos cólon no dia 12, de IL-1ß, TNF, IL-6, IL-17, KC e MIG dias 12 e 65, e IL-33, TGF e GM-CSF no dia 65 quando comparados a animais controle. Além disso, animais pós-sepse apresentaram maior quantidade de Treg no D15, contudo nos dias 12 e 65 observou-se um aumento significativo dessas células nos animais controle comparado ao pós-sepse. Curiosamente, animais pós-sepse que receberam CYP e DTX apresentaram colite e tumores de maneira semelhante aos animais controle. Por outro lado, camundongos pós-sepse tratados previamente com AOM/DSS apresentaram aumento na carga tumoral 30 dias após a CLP quando comparados aos controles. Além disso, no modelo de tumor subcutâneo e esplênico, foi observado maior crescimento tumoral em animais pós-sepse em comparação aos controles. Conclusões: A sepse promove inibição da inflamação intestinal murina e do CCR associado à colite, de maneira dependente de células Treg.

Introduction: Colorectal cancer (CRC) is the third most diagnosed neoplasm in the world. Inflammatory bowel disease is an important cause of CRC with pathogenesis linked to chronic inflammation. Sepsis is a life-threatening disease that modify the host immune response. We aimed to study whether sepsis-surviving mice showed alterations of colorectal cancer initiation and tumor progression. Materials and methods: C57Bl6 male mice were submitted to cecal ligation and puncture (CLP) model, and after 15 days, sepsis-surviving mice and one control group received azoxymethane (AOM, 10 mg/kg, ip) and dextran sodium sulfate (DSS 2%, ad libitum, 3 cycles of 5 days) on days 20-25, 40-45, 60-65 post-CLP. Colitis and tumor development were evaluated by colonoscopy. Cytokines were quantified on days 0, 12, 52 and 65 by Milliplex and Treg cells on days 12 and 65 by flow cytometry. Two groups of C57 animals received cyclophosphamide (CYP) (100 mg/kg, ip), and two groups of animals expressing diphtheria toxin (DTX) receptor under regulation of Foxp3 received DTX (0.5 mg/animal, ip) before the AOM/DSS protocol. Another animal cohort was submitted to CLP after receiving AOM/DSS, as well as, two other groups were injected with murine CRC cells (MC38luc) 105 cells subcutaneously or 106 cells intra-splenically 15 days post-CLP. Results: Sepsis-surviving animals showed reduced colitis, besides lower incidence, number of tumors and tumor load than control animals. Sepsis-surviving animals have lower production of IFN-γ in the colon on day 12, and of IL-1ß, TNF, IL-6, IL-17, KC and MIG on days 12 and 65, in addition to IL-33, TGF and GM-CSF on day 65 than control animals. In addition, post-sepsis mice had a higher amount of Treg on D15, however on days 12 and 65 a significant increase of these cells occurs in control animals compared to post-sepsis. Interestingly, post-sepsis animals receiving CYP and DTX developed colitis and tumors in a similar pattern as control animals. Conversely, post-sepsis mice previously submitted to OM/DSS showed an increase in tumor load 30 days after CLP when compared to controls. Furthermore, in the subcutaneous and intra-splenic model, it was observed increased tumor growth in post-sepsis animals when compared to the controls. Conclusions: Sepsis promotes inhibition of murine intestinal inflammation and colitis-associated CRC in a Treg dependent manner.
Descritores: Neoplasias Colorretais
Linfócitos T Reguladores
Colite
Sepse
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Id: biblio-1145410
Autor: Jadue A, Nicole; González A, Iván.
Título: Inmunopatogenia de las enfermedades autoinmunes / Immunophat ogenesis of aut oimmune diseases
Fonte: Rev. Méd. Clín. Condes;23(4):464-472, jul. 2012. tab.
Idioma: es.
Resumo: Las enfermedades autoinmunes son patologías de gran complejidad clínica, difícil diagnóstico y complejo tratamiento cuya etiología permanece aún desconocida pese a los múltiples avances realizados en los últimos años. En la génesis de estas enfermedades participan múltiples factores que conflyen entre sí para dar origen a cada una de las patologías autoinmunes conocidas, sean estas órgano-específicas o sistémicas. Entre estos elementos se incluyen la pérdida de los mecanismos de tolerancia, factores de susceptibilidad genética (polimorfismos HLA, genes no HLA y mecanismos epigenéticos), factores ambientales (agentes vivos de enfermedad, agentes inorgánicos, hormonas y otros) y factores inmunológicos (linfocitos reguladores, citoquinas y moléculas coestimulatorias, entre otros). La identificación de estos factores permitirá mejorar el conocimiento de los variados mecanismos que median estas complejas enfermedades, facilitando no sólo el entendimiento de su etiología sino también perfeccionar las herramientas terapéuticas para enfrentarlas.

Autoimmune diseases are pathologies of great clinical complexity, difficult diagnosis and treatment complex which etiology still remains unknowns despite the many advances made in recent years. In the genesis of these diseases involves multiple factors that converge together to give rise to each of the autoimmune diseases knows, whether organ specific or systemic. These elements include loss of tolerance mechanisms, genetic susceptibility factors (HLA polymorphisms, genes non-HLA and epigenetic mechanisms), environmental factors (living agents of disease, inorganic agents, hormones, etc.) and immunologic factors (regulators lymphocyte, cytokines, costimulatory molecules and others). Identifying these factors will improve the knowledge of the various mechanisms that mediate these complex diseases facilitating not only the understanding of the etiology but also improve the therapeutic tools to address them.
Descritores: Doenças Autoimunes/etiologia
Doenças Autoimunes/imunologia
Doenças Reumáticas/imunologia
-Linfócitos T Reguladores/imunologia
Predisposição Genética para Doença
Tolerância Central
Tolerância Imunológica
Limites: Humanos
Responsável: CL1.1 - Biblioteca Central



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