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

Chin, Alex; Flynn, Andrew N.; Fedwick, Jason P.; Buret, André G.

doi:10.1139/y06-056

Cited by 95 publications

(71 citation statements)

References 41 publications

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“…More specifically, it has been demonstrated that tight junctional proteins, ZO-1 and ZO-2 and occludin, are cleaved by caspase-3 [15]. The role of apoptosis in the potential increase of the BBB permeability by H. parasuis remains to be investigated, with the use, for example, of transwells as previously described [6].…”

Section: Discussionmentioning

confidence: 95%

Interactions ofHaemophilus parasuisand its LOS with porcine brain microvascular endothelial cells

et al. 2008

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-Haemophilus parasuis is a swine pathogen that causes Glässer's disease, which is characterized by polyserositis and meningitis. The pathogenesis of the H. parasuis infection is poorly understood. To cause meningitis, H. parasuis has to cross the blood-brain barrier (BBB) to gain access to the central nervous system (CNS). We recently showed that H. parasuis adheres to and invades porcine brain microvascular endothelial cells (PBMEC). The aim of this study was to evaluate the role of H. parasuis lipooligosaccharide (LOS) in the adhesion to PBMEC and to determine if H. parasuis (and/or its LOS) is able to induce apoptosis and activation of PBMEC. Results showed that adhesion of H. parasuis to PBMEC was partially mediated by LOS. Moreover, H. parasuis induces caspase-3-mediated apoptosis of PBMEC in a time -and dosedependent manner, but its LOS did not seem to be involved in such a process. Furthermore, H. parasuis and, to a lesser extent, its LOS, was able to induce the release of IL-8 and IL-6 by PBMEC. Field strains of H. parasuis serotypes 4 and 5 induced similar levels of these inflammatory mediators. Our data suggest that H. parasuis uses cellular adhesion, induction of apoptosis and up-regulation of inflammatory mediators as mechanisms to invade the CNS via the BBB, and that LOS would play a certain but limited role in such pathological process. Haemophilus parasuis / LOS / endothelial cells / BBB / meningitis

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Section: Discussionmentioning

confidence: 95%

Interactions ofHaemophilus parasuisand its LOS with porcine brain microvascular endothelial cells

et al. 2008

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“…Studies in the stratified squamous epithelium of the esophagus have presented evidence for the fact that acid stimulation disrupted the barrier function by modulating the amount and localization of TJ proteins in a cell culture model in vitro (3, 4, 25). Many studies in intestinal epithelial cell lines have also demonstrated that LPS could damage the intestinal epithelial barrier function by altering the TJ proteins expression and/or localization (5,13). Perhaps a more likely explanation is that, in the RE of goats, claudin-1 does not contribute to barrier function as it does in the colon (30) and esophagus (25) and that the loss of barrier function is due to the loss of claudin-4, occludin, and ZO-1.…”

Section: Discussionmentioning

confidence: 99%

A high-grain diet causes massive disruption of ruminal epithelial tight junctions in goats

Liu

et al. 2013

American Journal of Physiology-Regulatory, Integrative and Comp

162

167

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Alterations in rumen epithelial tight junctions (TJs) at the tissue and molecular levels during high-grain (HG) diet feeding are unknown. Here, 10 male goats were randomly assigned to either a hay diet (0% grain; n ϭ 5) or HG diet group (65% grain; n ϭ 5) to characterize the changes in ruminal epithelial structure and TJ protein expression and localization using scanning and transmission electron microscopy, quantitative real-time PCR, Western blot analysis, and immunofluorescence. After 7 wk of feeding, ruminal free LPS in HG group increased significantly (P Ͻ 0.001) compared with the hay group, and free LPS in the peripheral blood was detectable with concentrations of 0.8 Ϯ 0.20 EU/ml, while not detectable in the control, suggesting a leakage of LPS into the blood in the HG group. Correspondingly, the HG-fed goats showed profound alterations in ruminal epithelial structure and TJ proteins, depicted by marked epithelial cellular damage and intercellular junction erosion, down-regulation of TJ proteins claudin-4, occludin, and zonula occludens-1 mRNA and protein expression, as well as redistribution of claudin-1, claudin-4, and occludin. Furthermore, these changes in TJ proteins in the HG group were coupled with the upregulation of mRNA levels for the cytokines TNF-␣ and IFN-␥ in the ruminal epithelia. These results demonstrated for the first time that the HG diet feeding caused disruption of ruminal epithelial TJs that was associated with a local inflammatory response in the rumen epithelium. These findings may provide new insights into understanding the role of TJ proteins in the ruminal epithelial immune homeostasis of ruminants. rumen epithelium; high-grain diet; tight junction protein; lipopolysaccharide; inflammation IN CURRENT INTENSIVE RUMINANT production system, it has become common to use high-concentrate diets (high-grain, HG) to maximize energy intake and to improve milk production or daily weight gain, but highly fermentable diets can put the animal at risk. Rapidly fermentable nonstructural carbohydrates increase the rate of fermentation acid production in the rumen, and the accumulation of the acids leads to a decrease in ruminal pH, hyperosmolarity, and an increase in ruminal toxin concentration (2, 29). Previous studies have investigated the specific effect of low pH (9, 26), hyperosmolarity (20, 34), or an exposure to toxins (7) on ruminal epithelial barrier function in vitro. It should be acknowledged that any one or the combination of these factors may affect epithelial barrier function. In addition, the prominent histological alterations during HG feeding strongly suggest an impaired barrier function (35-37) that may provide the opportunity for the translocation of toxins and bacteria from the rumen into the blood, ultimately affecting animal health and productivity (28). Although there is fundamental knowledge about the consequences of HG feeding on ruminal epithelial barrier function, remarkably little information is currently available about the underlying molecular changes in ruminal epi...

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“…Additionally, we have shown that PAF does not only directly regulate apoptosis, but that signaling via the PAFR induces TLR4 expression in enterocytes (unpublished data). TLR4, the receptor for LPS, has been shown to take part in NEC pathogenesis [73,82], causes enterocyte apoptosis [101] and defective enterocyte migration [82]. Furthermore, TLR4 activation leads to induction of inflammatory molecules such as TNFα [102] and nitric oxide (NO) [103]; both of these molecules have been shown to be involved in NEC pathogenesis [15,81,104] and have been shown to be pro-apoptotic for enterocytes [81,105].…”

Section: Pro-apoptotic Signaling In Necmentioning

confidence: 99%

Intestinal Epithelial Cell Apoptosis, Immunoregulatory Molecules, and Necrotizing Enterocolitisb

Jilling¹

2012

J Clin Cell Immunol

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Necrotizing enterocolitis is one of the most severe, life-threatening consequences of premature birth, affecting 5-15% of premature neonates with birth weights <1,500 grams. Many lines of evidence suggest a role for the dysregulation of enterocyte apoptosis in NEC pathogenesis. In addition to apoptosis, the roles of several inflammatory mediators such as platelet-activating factor, IL-8, TNFα and endotoxin have been shown to be pathogenic. Receptors for these ligands and downstream cellular signaling pathways, such as mitochondrial injury-induced caspase activation and NFĸB-mediated transcriptional regulation are thought to be involved in the mechanisms of mucosal injury in NEC. In this review, we attempt to summarize the role of enterocyte apoptosis in NEC along with an analysis of the connection between inflammatory signaling and apoptosis in this disease.

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

Cited by 95 publications

References 41 publications

Interactions ofHaemophilus parasuisand its LOS with porcine brain microvascular endothelial cells

Interactions ofHaemophilus parasuisand its LOS with porcine brain microvascular endothelial cells

A high-grain diet causes massive disruption of ruminal epithelial tight junctions in goats

Intestinal Epithelial Cell Apoptosis, Immunoregulatory Molecules, and Necrotizing Enterocolitisb

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