5-Hydroxyeicosatetraenoic acid and leukotriene D4 increase intestinal epithelial paracellular permeability

<p><span style="color:rgb( 33 , 33 , 33 )">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...

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Autores: Rodríguez Lagunas, María José, Storniolo, Carolina Emilia, Ferrer i Roig, Ruth, Moreno Aznárez, Juan José
Formato: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2013
País:España
Recursos:Universidad de Barcelona
Repositorio:Dipòsit Digital de la UB
OAI Identifier:oai:diposit.ub.edu:2445/207663
Acesso em linha:https://hdl.handle.net/2445/207663
Access Level:acceso abierto
Palavra-chave:Càncer colorectal
Malalties inflamatòries intestinals
Colorectal cancer
Inflammatory bowel diseases
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spelling 5-Hydroxyeicosatetraenoic acid and leukotriene D4 increase intestinal epithelial paracellular permeabilityRodríguez Lagunas, María JoséStorniolo, Carolina EmiliaFerrer i Roig, RuthMoreno Aznárez, Juan JoséCàncer colorectalMalalties inflamatòries intestinalsColorectal cancerInflammatory bowel diseases<p><span style="color:rgb( 33 , 33 , 33 )">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.</span></p>Elsevier Ltd2013info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfhttps://hdl.handle.net/2445/207663Articles publicats en revistes (Nutrició, Ciències de l'Alimentació i Gastronomia)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésVersió postprint del document publicat a:International Journal of Biochemistry and Cell Biology, 2013(c) Elsevier Ltd, 2013info:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/2076632026-05-27T06:46:51Z
dc.title.none.fl_str_mv 5-Hydroxyeicosatetraenoic acid and leukotriene D4 increase intestinal epithelial paracellular permeability
title 5-Hydroxyeicosatetraenoic acid and leukotriene D4 increase intestinal epithelial paracellular permeability
spellingShingle 5-Hydroxyeicosatetraenoic acid and leukotriene D4 increase intestinal epithelial paracellular permeability
Rodríguez Lagunas, María José
Càncer colorectal
Malalties inflamatòries intestinals
Colorectal cancer
Inflammatory bowel diseases
title_short 5-Hydroxyeicosatetraenoic acid and leukotriene D4 increase intestinal epithelial paracellular permeability
title_full 5-Hydroxyeicosatetraenoic acid and leukotriene D4 increase intestinal epithelial paracellular permeability
title_fullStr 5-Hydroxyeicosatetraenoic acid and leukotriene D4 increase intestinal epithelial paracellular permeability
title_full_unstemmed 5-Hydroxyeicosatetraenoic acid and leukotriene D4 increase intestinal epithelial paracellular permeability
title_sort 5-Hydroxyeicosatetraenoic acid and leukotriene D4 increase intestinal epithelial paracellular permeability
dc.creator.none.fl_str_mv Rodríguez Lagunas, María José
Storniolo, Carolina Emilia
Ferrer i Roig, Ruth
Moreno Aznárez, Juan José
author Rodríguez Lagunas, María José
author_facet Rodríguez Lagunas, María José
Storniolo, Carolina Emilia
Ferrer i Roig, Ruth
Moreno Aznárez, Juan José
author_role author
author2 Storniolo, Carolina Emilia
Ferrer i Roig, Ruth
Moreno Aznárez, Juan José
author2_role author
author
author
dc.subject.none.fl_str_mv Càncer colorectal
Malalties inflamatòries intestinals
Colorectal cancer
Inflammatory bowel diseases
topic Càncer colorectal
Malalties inflamatòries intestinals
Colorectal cancer
Inflammatory bowel diseases
description <p><span style="color:rgb( 33 , 33 , 33 )">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.</span></p>
publishDate 2013
dc.date.none.fl_str_mv 2013
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/207663
url https://hdl.handle.net/2445/207663
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Versió postprint del document publicat a:
International Journal of Biochemistry and Cell Biology, 2013
dc.rights.none.fl_str_mv (c) Elsevier Ltd, 2013
info:eu-repo/semantics/openAccess
rights_invalid_str_mv (c) Elsevier Ltd, 2013
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier Ltd
publisher.none.fl_str_mv Elsevier Ltd
dc.source.none.fl_str_mv Articles publicats en revistes (Nutrició, Ciències de l'Alimentació i Gastronomia)
reponame:Dipòsit Digital de la UB
instname:Universidad de Barcelona
instname_str Universidad de Barcelona
reponame_str Dipòsit Digital de la UB
collection Dipòsit Digital de la UB
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,300719

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