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The role of caspase-3 in lipopolysaccharide-mediated disruption of intestinal epithelial tight junctions

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The mechanisms responsible for microbially induced epithelial apoptosis and increased intestinal permeability remain unclear. This study assessed whether purified bacterial lipopolysaccharide (LPS) increases epithelial apoptosis and permeability and whether these changes are dependent on caspase-3 activation. In nontumorigenic epithelial monolayers, Escherichia coli O26:B6 LPS increased apoptosis, as shown by nuclear breakdown, caspase-3 activation, and PARP cleavage, and induced disruption of tight junctional ZO-1. Apical, but not basolateral, exposure to LPS increased epithelial permeability. Addition of a caspase-3 inhibitor abolished the effects of LPS. The findings describe a novel mechanism whereby apical LPS may disrupt epithelial tight junctional ZO-1 and barrier function in a caspase-3-dependent fashion.

Les mécanismes responsables de l’apoptose épithéliale microbienne et de l’augmentation de la perméabilité intestinale sont encore mal connus. La présente étude a eu pour but de déterminer si le LPS bactérien purifié peut augmenter la perméabilité et l’apoptose épithéliales, et si ces modifications dépendent de l’activation de la caspase-3. Dans des monocouches épithéliales non tumorigènes, le LPS de Escherichia coli O26:B6 a augmenté l’apoptose, comme démontré par la dégradation nucléaire, l’activation de la caspase-3 et le clivage de la PARP, et a entraîné la rupture des protéines des jonctions serrées ZO-1. Une exposition apicale, mais pas basolatérale, au LPS a augmenté la perméabilité épithéliale. L’ajout d’un inhibiteur de caspase-3 a supprimé les effets du LPS. Les résultats décrivent un nouveau mécanisme par lequel le LPS apical pourrait interrompre ZO-1 des jonctions serrées et la fonction de barrière épithéliales d’une manière dépendante de la caspase-3.

Document Type: Research Article

Publication date: October 1, 2006

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  • Published since 1929, this monthly journal reports current research in all aspects of physiology, nutrition, pharmacology, and toxicology, contributed by recognized experts and scientists. It publishes symposium reviews and award lectures and occasionally dedicates entire issues or portions of issues to subjects of special interest to its international readership.
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