RESUMEN
The NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome plays an important role in a variety of diseases. However, the role of NLRP3 in the human intervertebral disc (IVD) degeneration remains unknown. In the present study, we assessed the expression levels of the NLRP3 inflammasome and its downstream targets caspase-1 and IL-1ß in 45 degenerate and seven nondegenerate IVD samples. The correlation between the degeneration scores and expression levels of NLRP3, caspase-1, and IL-1ß were also analyzed. The mRNA expression levels of the three molecules (NLRP3, caspase-1, and IL-1ß) were higher in the degenerate IVDs group than the controls (nondegenerate IVDs group). Immunohistochemistry showed that the expression levels of all three molecules were markedly increased in the nucleus pulposus of degenerate IVDs compared with nondegenerate IVDs. There was a positive correlation between the degeneration scores and the expression levels of the NLRP3 inflammasome as well as its downstream targets caspase-1 and IL-1ß. The findings suggest that excessive activation of the NLRP3 inflammasome results in overproduction of downstream IL-1ß, which participates in the pathogenesis of human IVD degeneration. Therefore, the NLRP3 inflammasome might serve as a potential therapeutic target for the prevention and treatment of IVD degeneration.
Asunto(s)
Proteínas Portadoras/metabolismo , Caspasa 1/metabolismo , Interleucina-1beta/metabolismo , Degeneración del Disco Intervertebral/metabolismo , Disco Intervertebral/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Inflamasomas/metabolismo , Disco Intervertebral/patología , Disco Intervertebral/cirugía , Degeneración del Disco Intervertebral/patología , Degeneración del Disco Intervertebral/cirugía , Dolor de la Región Lumbar/metabolismo , Dolor de la Región Lumbar/patología , Dolor de la Región Lumbar/cirugía , Vértebras Lumbares/metabolismo , Vértebras Lumbares/patología , Vértebras Lumbares/cirugía , Masculino , Persona de Mediana Edad , Proteína con Dominio Pirina 3 de la Familia NLR , Índice de Severidad de la Enfermedad , Fusión Vertebral , Resultado del Tratamiento , Adulto JovenRESUMEN
GMP reductase 2 from human has been expressed in Escherichia coli, purified and crystallized. The crystals belong to space group P3(2)21, with unit-cell parameters a = b = 110.6, c = 209.8 A, alpha = beta = 90, gamma = 120 degrees. Diffraction data were collected to 3.0 A with a completeness of 100% (100% for the last shell), an R(merge) value of 0.089 (0.189) and an I/sigma(I) value of 7.3 (3.2).