Navegando por Palavras-chave "Toll-like receptors"

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    Differential expression of toll-like receptor signaling cascades in LPS-tolerant human peripheral blood mononuclear cells
    (Elsevier B.V., 2011-03-01) Mendes, Marialice Erdelyi [UNIFESP]; Baggio-Zappia, Giovana Lotici [UNIFESP]; Colo Brunialti, Milena Karina [UNIFESP]; Fernandes, Maria da Luz [UNIFESP]; Rapozo, Marjorie Marini [UNIFESP]; Salomao, Reinaldo [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Pre-exposure to low doses of LPS induces resistance to a lethal challenge, a phenomenon known as endotoxin tolerance. in this study, tolerance was induced in human PBMC by culturing cells with 1 ng/mL LPS for 48 h. Cells were subsequently challenged with 100 ng/mL LPS for 2, 6 and 24 h, and the expression of 84 genes encoding proteins involved in the TLR signaling pathway was evaluated at each time point by PCR array. LPS pretreatment did not modulate the expression of TLR4 and CD14 on the surface of monocytes. A gene was defined as tolerized when LPS pretreatment reversed the effect of LPS challenge on the expression of the gene or as non-tolerized when LPS pretreatment did not reverse the effects of LPS challenge. We observed impaired signal transduction through the NF-kappa B, JNK, ERK and TRIF pathways, whereas expression of p38 pathway-related genes was preserved in LPS-tolerant cells. These results show a distinct regulation of the TLR pathway cascades during tolerance; this may account for the differential gene expression of some inflammatory mediators, such as up-regulation of IL-10 and COX2 as well as down-regulation of INF-alpha and IL-12. Depending on the effect of LPS-induced gene up-regulation or down-regulation, tolerance, as a reversion of such LPS effects, may result in repression or induction of gene expression. (C) 2010 Elsevier GmbH. All rights reserved.
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    Efeito do tratamento com Ginkgo biloba sobre a inflamação hipotalâmica presente em ratos com obesidade induzida pela dieta
    (Universidade Federal de São Paulo, 2015-11-27) Julio, Viviane da Silva [UNIFESP]; Telles, Monica Marques [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    It has been described that treatment with the standardized extract of Ginkgo biloba (EGb) promotes improvement of inflammatory conditions and this effect arises through inhibition of the Toll-like receptors. It is known that elevated circulating levels of saturated fatty acids that activates inflammatory pathway through the Toll-like receptor 4, promoting the expression of proinflammatory cytokines involved in obesity, such as hypothalamic inflammation. Therefore, the aim of this study was to analyze the effect of EGb on pathways of Toll-like receptor 4, serotonergic and hypothalamic neuropeptides of diet induced obesity (DIO) rats. The results showed no effect of EGb on the approaches. However, we observed in the EGb treated group a reduction in cumulative food consumption trend and a significant reduction in the total body weight gain over the period of treatment and in the mass of the retroperitoneal fat depot. Furthermore, the 5-HT1B levels and AgRP gene expression showed a decreasing trend in rats treated with EGb, these data could explain at least in part the reduced food intake observed in this study. The results regarding the reduction of body weight and visceral fat mass in obese animals, even maintaining high fat and high calorie diet during the herbal treatment, allow us to suggest that EGb represent an alternative therapy to prevent and / or treat obese people who have difficulties in getting used to a healthy diet and physical exercise. Therefore, it is necessary to elucidate the mechanisms of action of this herbal medicine on energy homeostasis.
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    Evaluation of Toll-like, chemokine, and integrin receptors on monocytes and neutrophils from peripheral blood of septic patients and their correlation with clinical outcomes
    (Associação Brasileira de Divulgação Científica, 2014-05-02) Silva, Selma Cristina da [UNIFESP]; Baggio-Zappia, Giovana Lotici [UNIFESP]; Brunialti, Milena Karina Coló [UNIFESP]; Assunçao, M.s.c.; Azevedo, Luciano Cesar Pontes [UNIFESP]; Machado, Flávia Ribeiro [UNIFESP]; Salomão, Reinaldo [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Hospital Israelita Albert Einstein Unidade de Terapia Intensiva; Hospital Sírio Libanês Unidade de Terapia Intensiva
    Recognition of pathogens is performed by specific receptors in cells of the innate immune system, which may undergo modulation during the continuum of clinical manifestations of sepsis. Monocytes and neutrophils play a key role in host defense by sensing and destroying microorganisms. This study aimed to evaluate the expression of CD14 receptors on monocytes; CD66b and CXCR2 receptors on neutrophils; and TLR2, TLR4, TLR5, TLR9, and CD11b receptors on both cell types of septic patients. Seventy-seven septic patients (SP) and 40 healthy volunteers (HV) were included in the study, and blood samples were collected on day zero (D0) and after 7 days of therapy (D7). Evaluation of the cellular receptors was carried out by flow cytometry. Expression of CD14 on monocytes and of CD11b and CXCR2 on neutrophils from SP was lower than that from HV. Conversely, expression of TLR5 on monocytes and neutrophils was higher in SP compared with HV. Expression of TLR2 on the surface of neutrophils and that of TLR5 on monocytes and neutrophils of SP was lower at D7 than at D0. In addition, SP who survived showed reduced expression of TLR2 and TLR4 on the surface of neutrophils at D7 compared to D0. Expression of CXCR2 for surviving patients was higher at follow-up compared to baseline. We conclude that expression of recognition and cell signaling receptors is differentially regulated between SP and HV depending on the receptor being evaluated.
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    Interactions between TLR2, TLR4, and mannose receptors with gp43 from Paracoccidioides brasiliensis induce cytokine production by human monocytes
    (Informa Healthcare, 2011-10-01) Nakaira-Takahagi, Erika; Golim, Marjorie A.; Bannwart, Camila F.; Puccia, Rosana [UNIFESP]; Peraçoli, Maria Terezinha Serrão [UNIFESP]; Universidade de São Paulo (USP); Universidade Federal de São Paulo (UNIFESP)
    The glycoprotein gp43 is an immunodominant antigen secreted by Paracoccidioides brasiliensis, the agent of paracoccidioidomycosis. the present study evaluated whether gp43 can interact with toll-like (TLR2, TLR4) and mannose (MR) receptors on the surface of human monocytes, and how that affects their expression and cytokine production. Monocytes were incubated with or without monoclonal antibodies anti-TLR2, anti-TLR4, or anti-MR, individually or in combination, prior to the addition of gp43. the gp43 binding to monocyte surface, as well as expression of TLR2, TLR4, and MRs were analyzed by flow cytometry, while production of TNF-alpha and IL-10 was monitored by ELISA. the results suggested that gp43 binds to TLR2, TLR4, and MR receptors, with TLR2 and MR having the strongest effect. All three receptors influenced the production of IL-10, while TNF-alpha production was associated with expression of TLR4 and MR. the modulatory effect of gp43 was demonstrated by high levels of TLR4 expression associated with increased production of TNF-alpha after 4 h of culture. Alternatively, high levels of TLR2 expression, and elevated production of IL-10, were detected after 18 h. We showed that interaction between gp43 and monocytes may affect the innate immune response by modulating the expression of the pattern recognition receptors TLR2, TLR4 and MR, as well as production of pro- and anti-inflammatory cytokines.
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    Sistema imunitário - parte II: fundamentos da resposta imunológica mediada por linfócitos T e B
    (Sociedade Brasileira de Reumatologia, 2010-10-01) Mesquita Júnior, Danilo [UNIFESP]; Araújo, Júlio Antônio Pereira; Catelan, Tânia Tieko Takao [UNIFESP]; Souza, Alexandre Wagner Silva de [UNIFESP]; Cruvinel, Wilson de Melo [UNIFESP]; Andrade, Luiz Eduardo Coelho [UNIFESP]; Silva, Neusa Pereira da [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    The immune system consists of an intricate network of organs, cells, and molecules responsible for maintaining the body's homeostasis and responding to aggression in general. Innate immunity operates in conjunction with adaptive immunity and is characterized by rapid response to aggression, regardless of previous stimulus, being the organism first line of defense. Its mechanisms include physical, chemical and biological barriers, cellular components, as well as soluble molecules. The organism first line of defense against tissue damage involves several steps closely integrated and constituted by different components of this system. The aim of this review is to restore the foundations of this response, which has high complexity and consists of several components that converge to articulate the development of adaptive immune response. We selected some of the following steps to review: perception and molecular recognition of aggressive agents; activation of intracellular pathways, which result in vascular and tissue changes; production of a myriad of mediators with local and systemic effects on cell activation and proliferation, synthesis of new products involved in the chemoattraction and migration of cells specialized in destruction and removal of offending agent; and finally, tissue recovery with restoration of functional tissue or organ.
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    Sistema imunitário: Parte I. Fundamentos da imunidade inata com ênfase nos mecanismos moleculares e celulares da resposta inflamatória
    (Sociedade Brasileira de Reumatologia, 2010-08-01) Cruvinel, Wilson de Melo [UNIFESP]; Mesquita Júnior, Danilo [UNIFESP]; Araújo, Júlio Antônio Pereira; Catelan, Tânia Tieko Takao [UNIFESP]; Souza, Alexandre Wagner Silva de [UNIFESP]; Silva, Neusa Pereira da [UNIFESP]; Andrade, Luiz Eduardo Coelho [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Pontifícia Universidade Católica de Goiás cursos de Medicina e Biomedicina
    The immune system consists of an intricate network of organs, cells, and molecules responsible for maintaining the body's homeostasis and responding to aggression in general. Innate immunity operates in conjunction with adaptive immunity and is characterized by rapid response to aggression, regardless of previous stimulus, being the organism first line of defense. Its mechanisms include physical, chemical and biological barriers, cellular components, as well as soluble molecules. The organism first line of defense against tissue damage involves several steps closely integrated and constituted by different components of this system. The aim of this review is to restore the foundations of this response, which has high complexity and consists of several components that converge to articulate the development of adaptive immune response. We selected some of the following steps to review: perception and molecular recognition of aggressive agents; activation of intracellular pathways, which result in vascular and tissue changes; production of a myriad of mediators with local and systemic effects on cell activation and proliferation, synthesis of new products involved in the chemoattraction and migration of cells specialized in destruction and removal of offending agent; and finally, tissue recovery with restoration of functional tissue or organ.
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    Sistema imunitário: parte III. O delicado equilíbrio do sistema imunológico entre os pólos de tolerância e autoimunidade
    (Sociedade Brasileira de Reumatologia, 2010-12-01) Souza, Alexandre Wagner Silva de [UNIFESP]; Mesquita Júnior, Danilo [UNIFESP]; Araújo, Júlio Antônio Pereira; Catelan, Tânia Tieko Takao [UNIFESP]; Cruvinel, Wilson de Melo [UNIFESP]; Andrade, Luiz Eduardo Coelho [UNIFESP]; Silva, Neusa Pereira da [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Pontifícia Universidade Católica de Goiás cursos de Medicina e Biomedicina
    The immune system consists of an intricate network of organs, cells, and molecules responsible for maintaining the body's homeostasis and responding to aggression in general. Innate immunity operates in conjunction with adaptive immunity and is characterized by rapid response to aggression, regardless of previous stimulus, being the organism first line of defense. Its mechanisms include physical, chemical and biological barriers, cellular components, as well as soluble molecules. The organism first line of defense against tissue damage involves several steps closely integrated and constituted by different components of this system. The aim of this review is to restore the foundations of this response, which has high complexity and consists of several components that converge to articulate the development of adaptive immune response. We selected some of the following steps to review: perception and molecular recognition of aggressive agents; activation of intracellular pathways, which result in vascular and tissue changes; production of a myriad of mediators with local and systemic effects on cell activation and proliferation, synthesis of new products involved in the chemoattraction and migration of cells specialized in destruction and removal of offending agent; and finally, tissue recovery with restoration of functional tissue or organ
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    Toll-like receptor pathway signaling is differently regulated in neutrophils and peripheral mononuclear cells of patients with sepsis, severe sepsis, and septic shock
    (Lippincott Williams & Wilkins, 2009-01-01) Salomao, Reinaldo [UNIFESP]; Brunialti, Milena K. C. [UNIFESP]; Gomes, Natalia E. [UNIFESP]; Mendes, Marialice E. [UNIFESP]; Diaz, Ricardo Sobhie [UNIFESP]; Komninakis, Shirley [UNIFESP]; Machado, Flavia R. [UNIFESP]; Silva, Ismael Dale Cotrim Guerreiro da [UNIFESP]; Rigato, Otelo [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Objectives: Up- and down-regulation of inflammatory response was described in blood cells from septic patients, according to the stage of sepsis and the cells evaluated. This study aimed to evaluate the Toll-like receptor (TLR) signaling pathway gene expression in peripheral blood mononuclear cells (PBMC) and neutrophils in patients throughout the different stages of sepsis.Design: Prospective, observational study.Settings. Two emergency rooms and two intensive care units in one university and one teaching hospital.Patients and Controls., A total of 15 septic patients, five with sepsis, five with severe sepsis, and five with septic shock, in addition to five healthy volunteers were enrolled.Interventions: None.Measurements and Main Results: the Human-TLR Signaling Pathway, which comprises 84 genes related to TLR-mediated signal transduction, was evaluated by real time polymerase chain reaction in PBMC and neutrophils obtained from patients and controls. the fold change for each gene (2((-Delta Delta Ct))) was compared between the groups. Genes with fold changes greater than 2 and significant changes in Delta CT are reported as differently expressed. the told change ratios in PBMC gene expression between septic patients and healthy controls revealed a dynamic process according to the stage of sepsis, tending toward down-regulation of the TLR signaling pathway in PBMC in the more severe forms of the disease. However, the differential gene expression was restricted to five down-regulated genes in septic shock patients, which are found in the effector and downstream pathways. Neutrophils showed a different pattern of adaptation. Patients with sepsis, severe sepsis, and septic shock presented a broad gene upregulation, which included all functional groups evaluated and persisted throughout the stages of the disease.Conclusions: TLR-signaling pathway genes are differently regulated in PBMC and neutrophils of septic patients, and are dynamically modulated throughout the different stages of sepsis. (Grit Care Med 2009; 37:132-139)