INVESTIGADORES
RUPIL Lucia Lara
congresos y reuniones científicas
Título:
DIAZEPAM EFFECTS ON IMMUNE CELLS ACTIVELY INVOLVED DURING THE DEVELOPMENT OF EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS
Autor/es:
FERNÁNDEZ HURST NICOLÁS; FALCÓN CRISTIAN; RUPIL LUCÍA LARA; CERVI LAURA; MONFERRAN CLARA; ROTH GERMAN
Lugar:
Medellín
Reunión:
Congreso; 11th Congress of the Latin American Association of Immunology ALAI; 2015
Resumen:
Benzodiazepines (Bz) are classically known to be psychoactive drugs that share pharmacological properties of tranquilizers, such as anxiolytic, sedative, hypnotic, skeletal muscle relaxant and anticonvulsant effects. This action is mediated by the central benzodiazepine receptor (CBR), also known as GABAA receptor. Bz have an alternative site of binding named peripheral benzodiazepine receptor (PBR), also named Translocator protein 18 kDa (TSPO). This receptor is neither structurally related nor coupled to the GABAA receptor, and is abundantly expressed in endocrine organs, skin, heart, lung epithelium, bone narrow, liver, spleen and to a lesser extent in the central nervous system (CNS), where it is associated with glial cells. It is also expressed in immune cells and action of Bz through PBR have been related to some modulatory properties on immune system functions. On the other hand, experimental autoimmune encephalomyelitis (EAE) is an animal model that mimics many of the clinical and pathological features of the human disease, multiple sclerosis (MS). Both, MS and EAE, have innate and adaptive immune responses against CNS antigens leading to inflammatory pathology. EAE can be induced in genetically susceptible animals by a single injection of CNS antigens homogenized in an adequate adjuvant. Wistar rats develop a monophasic course of the disease (acute stage) 11-13 days post-induction (dpi) characterized by ataxia and hind limb paralysis associated with weight loss and fecal and urinary incontinence. We have previously demonstrated that rats challenged for EAE and treated with low doses (0.1 mg/kg/day) of Dz showed reduced incidence and clinical signs of the disease. Concomitantly, Dz diminished several immunological parameters of the disease such as delayed-type hypersensitivity (DTH) reaction, specific lymphocyte proliferation against the encephalitogenic myelin basic protein (MBP), anti-MBP antibody production and spinal cord histological lesions associated with the disease. However, the molecular mechanism and cells involved in the reduction of the autoreactive inflammatory responses remains unclear. The aim of the present work was to evaluate the direct effect of Dz on different immune cells that participate in EAE development. Dendritic cells (DC) are key to the beginning of antigen specific responses and the state of activation achieved by them defines the type of response that will be generated. During the development of EAE, immature DC take the encephalitogenic CNS antigens and migrate to closer lymphatic nodes to enable naïve T lymphocytes to initiate immune cell responses. We evaluated the effect of Dz on the activation of DC. DC were differentiated from bone narrow of C57BL/6 mice and treated with several concentrations of Dz (5-100 μM) in the presence or absence of lipopolysaccharide (LPS). Dz did not affect the viability of resting or stimulated DC at any dose assayed. However, it was observed a reduction in the percentage of cells expressing MHCII and CD40 when DC were stimulated with LPS in the presence of Dz. In addition, Dz also significantly reduced the production of pro-inflammatory cytokines such as IL-12, IL-6 and TNF-α (p
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