RESUMEN
In the present study, we determined the significance of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) in Alzheimer's disease (AD). We characterized the expression of TRAIL protein in the cerebrospinal fluid (CSF) and serum with ELISA and TRAIL mRNA in the peripheral blood mononuclear cells (PBMCs) with real-time PCR in 22 patients with AD and 20 control cases. We could not find TRAIL protein in the CSF samples. The concentration of TRAIL protein in sera from patients with AD was not different from controls. However, there was an inverse correlation between serum TRAIL levels and Mini-Mental State Examination scores in AD patients. Also we did not find significant difference in TRAIL mRNA in the PBMCs of patients with AD when compared with control group. Our data indicate that TRAIL serum level decreases in the late stage of disease.
Asunto(s)
Enfermedad de Alzheimer/metabolismo , Ligando Inductor de Apoptosis Relacionado con TNF/metabolismo , Anciano , Enfermedad de Alzheimer/sangre , Enfermedad de Alzheimer/líquido cefalorraquídeo , Biomarcadores/sangre , Biomarcadores/líquido cefalorraquídeo , Estudios de Casos y Controles , Femenino , Humanos , Leucocitos Mononucleares/metabolismo , Masculino , Escala del Estado Mental , Persona de Mediana Edad , ARN Mensajero/análisis , Valores de Referencia , Estadísticas no Paramétricas , Ligando Inductor de Apoptosis Relacionado con TNF/sangre , Ligando Inductor de Apoptosis Relacionado con TNF/líquido cefalorraquídeo , Ligando Inductor de Apoptosis Relacionado con TNF/genéticaRESUMEN
Apart from potential roles in anti-tumor surveillance, the TNF-related apoptosis-inducing ligand (TRAIL) has important regulatory functions in the host immune response. We studied antiinflammatory effects of endogenous and recombinant TRAIL (rTRAIL) in experimental meningitis. Following intrathecal application of pneumococcal cell wall, a TLR2 ligand, we found prolonged inflammation, augmented clinical impairment, and increased apoptosis in the hippocampus of TRAIL(-/-) mice. Administration of rTRAIL into the subarachnoid space of TRAIL(-/-) mice or reconstitution of hematopoiesis with wild-type bone marrow cells reversed these effects, suggesting an autoregulatory role of TRAIL within the infiltrating leukocyte population. Importantly, intrathecal application of rTRAIL in wild-type mice with meningitis also decreased inflammation and apoptosis. Moreover, patients suffering from bacterial meningitis showed increased intrathecal synthesis of TRAIL. Our findings provide what we believe is the first evidence that TRAIL may act as a negative regulator of acute CNS inflammation. The ability of TRAIL to modify inflammatory responses and to reduce neuronal cell death in meningitis suggests that it may be used as a novel antiinflammatory agent in invasive infections.