Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 3 de 3
Filtrar
Mais filtros

Base de dados
Ano de publicação
Tipo de documento
País de afiliação
Intervalo de ano de publicação
1.
Front Immunol ; 12: 671511, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34054847

RESUMO

Multiple Sclerosis (MS) is a neuroinflammatory and chronic Central Nervous System (CNS) disease that affects millions of people worldwide. The search for more promising drugs for the treatment of MS has led to studies on Sildenafil, a phosphodiesterase type 5 Inhibitor (PDE5I) that has been shown to possess neuroprotective effects in the Experimental Autoimmune Encephalomyelitis (EAE), an animal model of MS. We have previously shown that Sildenafil improves the clinical score of EAE mice via modulation of apoptotic pathways, but other signaling pathways were not previously covered. Therefore, the aim of the present study was to further investigate the effects of Sildenafil treatment on autophagy and nitrosative stress signaling pathways in EAE. 24 female C57BL/6 mice were divided into the following groups: (A) Control - received only water; (B) EAE - EAE untreated mice; (C) SILD - EAE mice treated with 25mg/kg of Sildenafil s.c. The results showed that EAE mice presented a pro-nitrosative profile characterized by high tissue nitrite levels, lowered levels of p-eNOS and high levels of iNOS. Furthermore, decreased levels of LC3, beclin-1 and ATG5, suggests impaired autophagy, and decreased levels of AMPK in the spinal cord were also detected in EAE mice. Surprisingly, treatment with Sildenafil inhibited nitrosative stress and augmented the levels of LC3, beclin-1, ATG5, p-CREB and BDNF and decreased mTOR levels, as well as augmented p-AMPK. In conclusion, we propose that Sildenafil alleviates EAE by activating autophagy via the eNOS-NO-AMPK-mTOR-LC3-beclin1-ATG5 and eNOS-NO-AMPK-mTOR-CREB-BDNF pathways in the spinal cord.


Assuntos
Autofagia/efeitos dos fármacos , Encefalomielite Autoimune Experimental/patologia , Inibidores da Fosfodiesterase 5/farmacologia , Citrato de Sildenafila/farmacologia , Medula Espinal/efeitos dos fármacos , Animais , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Fármacos Neuroprotetores/farmacologia , Estresse Nitrosativo/efeitos dos fármacos
2.
Int Immunopharmacol ; 63: 84-93, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30075432

RESUMO

Dendritic cells (DCs) are antigen-presenting cells with the ability to activate naïve T cells and direct the adaptive cellular immune response toward a specific profile. This is important, as different pathogens demand specific "profiles" of immune responses for their elimination. Such a goal is achieved depending on the maturation/activation status of DCs by the time of antigen presentation to T cells. Notwithstanding this, recent studies have shown that DCs alter their metabolic program to accommodate the functional changes in gene expression and protein synthesis that follow antigen recognition. In this review, we aim to summarize the data in the literature regarding the metabolic pathways involved with DC phenotypes and their functions.


Assuntos
Células Dendríticas/metabolismo , Animais , Células Dendríticas/imunologia , Humanos , Transdução de Sinais
3.
Immunol Lett ; 196: 91-102, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29427742

RESUMO

Dendritic cells (DCs) are essential players in the activation of T cells and in the development of adaptive immune response towards invading pathogens. Upon antigen (Ag) recognition of Pathogen Associated Molecular Patterns (PAMPs) by their receptors (PRRs), DCs are activated and acquire an inflammatory profile. DCs have the ability to direct the profile of helper T (Th) cells towards Th1, Th2, Th17, Th9 and regulatory (Treg) cells. Each subset of Th cells presents a unique gene expression signature and is endowed with the ability to conduct or suppress effector cells in inflammation. Pathogens target DCs during infection. Many studies demonstrated that antigens and molecules derived from pathogens have the ability to dampen DC maturation and activation, leading these cells to a permissive state or tolerogenic profile (tolDCs). Although tolDCs may represent a hindrance in infection control, they could be positively used to modulate inflammatory disorders, such as autoimmune diseases. In this review, we focus on discussing findings that use pathogen-antigen modulated DCs and tolDCs in prophylactics and therapeutics approaches for vaccination against infectious diseases or inflammatory disorders.


Assuntos
Imunidade Adaptativa/imunologia , Antígenos/imunologia , Células Dendríticas/imunologia , Linfócitos T Reguladores/imunologia , Animais , Diferenciação Celular/imunologia , Humanos , Tolerância Imunológica/imunologia , Inflamação/imunologia , Linfócitos T Auxiliares-Indutores/imunologia , Linfócitos T Reguladores/citologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA