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1.
Nat Commun ; 14(1): 3804, 2023 06 26.
Artículo en Inglés | MEDLINE | ID: mdl-37365163

RESUMEN

The interleukin-1 family members, IL-1ß and IL-18, are processed into their biologically active forms by multi-protein complexes, known as inflammasomes. Although the inflammasome pathways that mediate IL-1ß processing in myeloid cells have been defined, those involved in IL-18 processing, particularly in non-myeloid cells, are still not well understood. Here we report that the host defence molecule NOD1 regulates IL-18 processing in mouse epithelial cells in response to the mucosal pathogen, Helicobacter pylori. Specifically, NOD1 in epithelial cells mediates IL-18 processing and maturation via interactions with caspase-1, instead of the canonical inflammasome pathway involving RIPK2, NF-κB, NLRP3 and ASC. NOD1 activation and IL-18 then help maintain epithelial homoeostasis to mediate protection against pre-neoplastic changes induced by gastric H. pylori infection in vivo. Our findings thus demonstrate a function for NOD1 in epithelial cell production of bioactive IL-18 and protection against H. pylori-induced pathology.


Asunto(s)
Células Epiteliales , Infecciones por Helicobacter , Interleucina-18 , Proteína Adaptadora de Señalización NOD1 , Animales , Ratones , Células Epiteliales/metabolismo , Infecciones por Helicobacter/metabolismo , Helicobacter pylori , Inflamasomas/metabolismo , Interleucina-18/metabolismo , Interleucina-1beta/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Transducción de Señal , Proteína Adaptadora de Señalización NOD1/metabolismo
2.
Sci Rep ; 6: 24280, 2016 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-27067957

RESUMEN

Recent developments in biological X-ray microscopy have allowed structural information and elemental distribution to be simultaneously obtained by combining X-ray ptychography and X-ray fluorescence microscopy. Experimentally, these methods can be performed simultaneously; however, the optimal conditions for each measurement may not be compatible. Here, we combine two distinct measurements of ultrastructure and elemental distribution, with each measurement performed under optimised conditions. By combining optimised ptychography and fluorescence information we are able to determine molar concentrations from two-dimensional images, allowing an investigation into the interactions between the environment sensing filopodia in fibroblasts and extracellular calcium. Furthermore, the biological ptychography results we present illustrate a point of maturity where the technique can be applied to solve significant problems in structural biology.


Asunto(s)
Elementos Químicos , Matriz Extracelular/química , Fibroblastos/ultraestructura , Procesamiento de Imagen Asistido por Computador/métodos , Microscopía/métodos , Espectrometría por Rayos X/métodos , Difracción de Rayos X/métodos , Animales , Células Cultivadas , Ratones
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