Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 5 de 5
Filtrar
Mais filtros










Base de dados
Tipo de estudo
Intervalo de ano de publicação
1.
Microbes Infect ; 22(10): 585-591, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32882412

RESUMO

Viral egress and autophagy are two mechanisms that seem to be strictly connected in Herpesviruses's biology. Several data suggest that the autophagic machinery facilitates the egress of viral capsids and thus the production of new infectious particles. In the Herpesvirus family, viral nuclear egress is controlled and organized by a well conserved group of proteins named Nuclear Egress Complex (NEC). In the case of EBV, NEC is composed by BFRF1 and BFLF2 proteins, although the alterations of the nuclear host cell architecture are mainly driven by BFRF1, a multifunctional viral protein anchored to the inner nuclear membrane of the host cell. BFRF1 shares a peculiar distribution with several nuclear components and with them it strictly interacts. In this study, we investigated the possible role of BFRF1 in manipulating autophagy, pathway that possibly originates from nucleus, regulating the interplay between autophagy and viral egress.


Assuntos
Autofagia , Herpesvirus Humano 4/fisiologia , Proteínas de Membrana/metabolismo , Proteínas Virais/metabolismo , Células HEK293 , Humanos , Lamina Tipo B/metabolismo , Proteínas Associadas aos Microtúbulos/metabolismo , Membrana Nuclear/metabolismo , Ligação Proteica , Liberação de Vírus , Proteínas rab de Ligação ao GTP/metabolismo , proteínas de unión al GTP Rab7
2.
Biochim Biophys Acta ; 1862(4): 805-813, 2016 04.
Artigo em Inglês | MEDLINE | ID: mdl-26769359

RESUMO

Type 2 is the type of diabetes with higher prevalence in contemporary time, representing about 90% of the global cases of diabetes. In the course of diabetes, several complications can occur, mostly due to hyperglycemia and increased reactive oxygen species (ROS) production. One of them is represented by an increased susceptibility to microbial infections and by a reduced capacity to clear them. Therefore, knowing the impact of hyperglycemia on immune system functionality is of utmost importance for the management of the disease. In this study, we show that medium containing high glucose reduced the in-vitro differentiation of monocytes into functional DCs and their activation mediated by PAMPs or DAMPs. Most importantly, the same effects were mediated by the hyperglycemic sera derived by type 2 diabetic patients, mimicking a more physiologic condition. DC dysfunction caused by hyperglycemia may be involved in the inefficient control of infections observed in diabetic patients, given the pivotal role of these cells in both the innate and adaptive immune response. Searching for the molecular mechanisms underlying DC dysfunction, we found that canonical Wnt/ß-catenin and p38 MAPK pathways were activated in the DCs differentiated either in the presence of high glucose or of hyper-glycemic sera. Interestingly, the activation of these pathways and the DC immune dysfunction were partially counteracted by the anti-oxidant quercetin, a flavonoid already known to exert several beneficial effects in diabetes.


Assuntos
Diferenciação Celular/imunologia , Células Dendríticas/imunologia , Diabetes Mellitus Tipo 2/imunologia , Sistema de Sinalização das MAP Quinases/imunologia , Espécies Reativas de Oxigênio/imunologia , Via de Sinalização Wnt/imunologia , Proteínas Quinases p38 Ativadas por Mitógeno/imunologia , Glicemia , Linhagem Celular , Células Dendríticas/patologia , Diabetes Mellitus Tipo 2/patologia , Humanos , Soro , beta Catenina/imunologia
3.
Biochim Biophys Acta ; 1843(7): 1348-55, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24726834

RESUMO

Autophagy has a pivotal role in the in-vitro monocyte differentiation into macrophages and dendritic cells (DCs), the most powerful antigen presenting cells (APC) with the unique capacity to initiate an adaptive immune response. Autophagy is also a mechanism by which these cells of innate immunity may degrade intracellular pathogens and mediate the antigen processing and presentation, essential to clear an infection. For these reasons, pathogens have learned how to manipulate autophagy for their own survival. In this study we found that hepatitis C virus (HCV), derived from sera of infected patients, blocked the autophagic process in differentiating monocytes, seen as LC3 II and p62 expression levels. The suppression of autophagy correlated with a reduction of cathepsins D, B and proteolytic activity, and resulted in impairment of monocyte differentiation into DCs, as indicated by the reduction of CD1a acquirement. These data suggest that the block of autophagy might be one of the underlying mechanisms of the HCV-mediated immune subversion that frequently leads to viral persistence and chronic hepatitis.


Assuntos
Antígenos Virais/farmacologia , Autofagia/efeitos dos fármacos , Células Dendríticas/virologia , Hepacivirus/imunologia , Soros Imunes/farmacologia , Monócitos/virologia , Imunidade Adaptativa , Apresentação de Antígeno , Antígenos CD1/genética , Antígenos CD1/imunologia , Antígenos Virais/imunologia , Autofagia/imunologia , Catepsina B/genética , Catepsina B/imunologia , Catepsina D/genética , Catepsina D/imunologia , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Células Dendríticas/imunologia , Células Dendríticas/patologia , Expressão Gênica , Hepatite C Crônica/imunologia , Hepatite C Crônica/patologia , Hepatite C Crônica/virologia , Interações Hospedeiro-Patógeno , Humanos , Evasão da Resposta Imune , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/imunologia , Monócitos/imunologia , Monócitos/patologia
4.
Oncol Rep ; 29(5): 1999-2004, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23446663

RESUMO

The Na+ ionophore monensin affects cellular pH and, depending on its concentration, causes the survival or death of tumor cells. In the present study, we elucidated the survival pathway activated in U937 cells, a human lymphoma-derived cell line. These cells treated with monensin at a concentration of 5 µM were growth-arrested in G1, activated p38 mitogen-activated protein kinase (MAPK) and showed an increased expression of cyclooxygenase-2 (COX-2). The latter two molecular events were linked, as pharmacological inhibition of the MAPK did not allow COX-2 increased expression. Furthermore, we showed that p38 and COX-2 keep monensin-stressed U937 cells alive, as pharmacological inhibition of each enzyme caused cell death.


Assuntos
Sobrevivência Celular/genética , Ciclo-Oxigenase 2/biossíntese , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/genética , Morte Celular/efeitos dos fármacos , Morte Celular/genética , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Indução Enzimática , Fase G1/efeitos dos fármacos , Fase G1/genética , Humanos , Monensin/farmacologia , Transdução de Sinais , Células U937 , Proteínas Quinases p38 Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases p38 Ativadas por Mitógeno/genética
5.
Virol J ; 9: 92, 2012 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-22583958

RESUMO

BACKGROUND: For an efficient immune response against viral infection, dendritic cells (DCs) must express a coordinate repertoire of receptors that allow their recruitment to the sites of inflammation and subsequently to the secondary lymphoid organs in response to chemokine gradients.Several pathogens are able to subvert the chemokine receptor expression and alter the migration properties of DCs as strategy to escape from the immune control. FINDINGS: Here we report the inhibitory effect of Human Herpesvirus 8 (HHV-8) on the migratory behavior of immature and mature DCs. We found that the virus altered the DC chemokine receptor expression and chemokine induced migration. Moreover HHV-8 was also able to interfere with basal motility of DCs by inducing cytoskeleton modifications. CONCLUSION: Based on our findings, we suggest that HHV-8 is able to subvert the DC migration capacity and this represents an additional mechanism which interferes with their immune-functions.


Assuntos
Movimento Celular , Citoesqueleto/metabolismo , Células Dendríticas/imunologia , Herpesvirus Humano 8/imunologia , Receptores CCR6/biossíntese , Receptores CCR7/biossíntese , Células Dendríticas/virologia , Regulação para Baixo , Herpesvirus Humano 8/patogenicidade , Humanos , Evasão da Resposta Imune
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...