RESUMEN
The loss of epithelial barrier function plays a crucial role in the pathogenesis of inflammatory bowel disease, with levels of 5-lipoxygenase metabolites being increased in the mucosa of these patients. The objective of this study was to determine the effect of the eicosanoids produced by the 5-lipoxygenase pathway, leukotriene B4 and D4, and 5-hydroxyeicosatetraenoic acid on epithelial barrier function. Paracellular permeability was estimated from fluorescein isothiocyanate-dextran fluxes and transepithelial electrical resistance in differentiated Caco-2 cells. Our results suggest that leukotriene D4 and 5-hydroxyeicosatetraenoic acid altered both parameters. Identification of the receptors involved in these changes indicated that cysteinyl-leukotriene receptor 1 participates in the effects of leukotriene D4. For both eicosanoids, these effects were mediated by activation of the phospholipase C/Ca(2+)/protein kinase C pathway, in addition to cAMP-independent protein kinase A activation. Furthermore, we observed a correlation between increased paracellular permeability and the redistribution of occludin, and for leukotriene D4, the disorganization of the subapical actin ring and myosin light chain kinase activation. In conclusion, on the basis of our results, we propose that 5-lipoxygenase pathway metabolites participate in the disruption of epithelial barrier function that is characteristic of inflammatory bowel disease.
Asunto(s)
Araquidonato 5-Lipooxigenasa/metabolismo , Ácidos Hidroxieicosatetraenoicos/metabolismo , Mucosa Intestinal/metabolismo , Leucotrieno D4/metabolismo , Uniones Estrechas/metabolismo , Células CACO-2 , Línea Celular Tumoral , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Cisteína , Impedancia Eléctrica , Epitelio/metabolismo , Humanos , Enfermedades Inflamatorias del Intestino/metabolismo , Leucotrienos , Ocludina/metabolismo , Permeabilidad , Proteína Quinasa C/metabolismo , Fosfolipasas de Tipo C/metabolismoRESUMEN
La Unidad de Laboratorios Docentes (ULD) de la Facultad de Farmacia (UB) ha implantado unsistema de gestión de la calidad (SGC) que permite transmitir al estudiante una formación adicionalcon el objetivo de mejorar sus competencias transversales (siguiendo las directrices del EspacioEuropeo de Educación Superior, EEES). Además, en el curso académico 06-07, se instauraron lasBuenas Prácticas Ambientales (BPAL) para disponer de un sistema de gestión que incorporase loscriterios de calidad, medioambiente y seguridad (sistema de gestión integrada, SGI). Durante elpresente curso académico se ha procedido a la grabación y edición de un video sobre calidad,seguridad y medioambiente en la ULD con el objetivo de mejorar la formación transversal de losestudiantes facilitando la integración de los conocimientos y habilidades profesionales. De esta forma,al salir del entorno universitario, los licenciados y graduados de la Facultad de Farmacia dispondrán deun valor añadido en su formación, mejorando así sus competencias para el desarrollo de su futuraprofesión. En el video se muestra la manera de trabajar correctamente según las normas de calidad,seguridad y medioambiente recogidas además en un tríptico que se entrega a los estudiantes al accederpor primera vez a un laboratorio de prácticas. El video se difundirá a través de la página web de laULD, de la videoteca de la UB, del canal You Tube Canal UB, así como de las asignaturas que losoliciten (sirviendo de soporte para el personal docente)(AU)
The Teaching Laboratories Unit (ULD) of the Faculty of Pharmacy (UB) has implemented amanagement system (QMS) that allows the student to get an additional training in order to improvetheir generic skills (following the guidelines of the Area European Higher Education Area, EHEA).Furthermore, in the 2006-2007 academic year, were introduced the Good Laboratory Practice (GLP)to have a management system that incorporates the criteria of quality, environment and security(integrated management system, IMS). During the present academic year it has been carried out therecording and editing of a video on quality, safety and environment in the ULD with the aim ofimproving cross-training of students by facilitating the integration of knowledge and professionalskills. Thus, on leaving the university, graduates in Pharmacy will have an added value in theirtraining, and thereby improving their skills for the development of their future profession. The videoshows how to work correctly according to the standards of quality, safety and environment that arealso contained in a leaflet that is given to students when they first access to a laboratory. The video will be disseminated through the website of the ULD, the library of the UB, the You Tube UB Canaland upon request(AU)