A New Principle for Tight Junction Modulation Based on Occludin Peptides

Tavelin, Staffan; Hashimoto, Kei; Malkinson, John P.; Lazorova, Lucia; Tóth, István; Artursson, Per

doi:10.1124/mol.64.6.1530

Cited by 105 publications

(75 citation statements)

References 37 publications

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“…Cells treated with occludin peptide for 30 minutes were used as a positive control. Occludin peptide treatment induced a 44-48% reduction in R T compared with mediumtreated controls, consistent with earlier studies (28,29). For negative controls (cells treated with either medium or sham), bacteria were not recovered from the basolateral media until 12 hours after adding the bacteria (Table 2).…”

Section: Rv Increases Bacterial Binding To and Transmigration Across supporting

confidence: 78%

Rhinovirus Disrupts the Barrier Function of Polarized Airway Epithelial Cells

Sajjan¹,

Wang²,

Zhao³

et al. 2008

Am J Respir Crit Care Med

304

312

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Rationale : Secondary bacterial infection following rhinovirus (RV) infection has been recognized in chronic obstructive pulmonary disease. Objectives: We sought to understand mechanisms by which RV infection facilitates secondary bacterial infection. Methods : Primary human airway epithelial cells grown at air-liquid interface and human bronchial epithelial (16HBE14o-) cells grown as polarized monolayers were infected apically with RV. Transmigration of bacteria (nontypeable Haemophilus influenzae and others) was assessed by colony counting and transmission electron microscopy. Transepithelial resistance (R T ) was measured by using a voltmeter. The distribution of zona occludins (ZO)-1 was determined by immunohistochemistry and immunoblotting. Measurements and Main Results : Epithelial cells infected with RV showed 2-log more bound bacteria than sham-infected cultures, and bacteria were recovered from the basolateral media of RV-but not sham-infected cells. Infection of polarized airway epithelial cell cultures with RV for 24 hours caused a significant decrease in R T without causing cell death or apoptosis. Ultraviolet-treated RV did not decrease R T , suggesting a requirement for viral replication. Reduced R T was associated with increased paracellular permeability, as determined by flux of fluorescein isothiocyanate (FITC)-inulin. Neutralizing antibodies to tumor necrosis factor (TNF)-a, IFN-g and IL-1b reversed corresponding cytokine-induced reductions in R T but not that induced by RV, indicating that the RV effect is independent of these proinflammatory cytokines. Confocal microscopy and immunoblotting revealed the loss of ZO-1 from tight junction complexes in RV-infected cells. Intranasal inoculation of mice with RV1B also caused the loss of ZO-1 from the bronchial epithelium tight junctions in vivo. Conclusions: RV facilitates binding, translocation, and persistence of bacteria by disrupting airway epithelial barrier function.

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Section: Rv Increases Bacterial Binding To and Transmigration Across supporting

confidence: 78%

Rhinovirus Disrupts the Barrier Function of Polarized Airway Epithelial Cells

Sajjan¹,

Wang²,

Zhao³

et al. 2008

Am J Respir Crit Care Med

304

312

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“…These findings collectively corroborate that BBB dysfunction is associated with increased permeability only to small molecules like water and ammonia but is not necessarily associated with a structural breakdown. Recent data from other laboratories have demonstrated that a leaky BBB could result from subtle alterations in the tight junction (Wong and Gumbiner, 1997;Tavelin et al, 2003;Nusrat et al, 2000;Nitta et al, 2003). Therefore, our results suggest that the pathogenesis of ALF-induced brain edema is unlike the brain edema caused by brain ischemia and traumatic brain injury, which result from complete BBB breakdown associated with the vasogenic mechanism, but likely involves a rather subtle disruption in the BBB.…”

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confidence: 43%

Subtle BBB alterations in brain edema associated with acute liver failure

Nguyen

2010

Neurochemistry International

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Vasogenic mechanism of brain edema in acute liver failure (ALF) remains poorly understood. Recent work demonstrates that matrix metalloproteinase-9 (MMP-9) contributes to the development of brain edema in experimental ALF (J Hepatol 44:1105(J Hepatol 44: , 2006. Importantly, MMP-9 blockage with specific monoclonal antibodies and/or synthetic inhibitor, the edema is attenuated. Specifically, utrastructural evaluations demonstrate intact blood-brain barrier and its tight junction. These results suggest that subtle alterations in BBB are likely to involve in the brain edema associated with ALF. KeywordsBlood-brain barrier; Brain edema; Acute liver failure Dear Editors, I have read the article (Sawara et al., 2009) with great interest. However, I would like to call your attention to the statement in the article, "In contrast to the present study, azoxymethane-treated mice manifest clear signs of physical breakdown of the BBB including extravasation of sodium fluorescein and Evans blue." We believe this is an incorrect interpretation of the cited work.In our report, "Matrix metalloproteinase-9 contributes to the brain extravasation and edema in fulminant hepatic failure mice," (Nguyen et al., 2006) we demonstrated the first evidence that a vasogenic mechanism takes part in the development of brain edema in acute liver failure (ALF). The original characterization of this mouse model of ALF by Matkowskyj et al. (1999) and recent further examination of this model by Dr. Butterworth's lab confirmed that this mouse model recapitulates the ALF in humans (Belanger et al., 2006). We further demonstrated the increased BBB permeability to Evans blue dye and water in azoxymethane-induced ALF in mice (Nguyen et al., 2006). The leakage of Evans blue was visualized as brain extravasation. When we examined the brains under fluorescent microscopy, the extravasated dye was observed in the immediate surrounding region of the brain capillary. More importantly, the electron microscopic evaluations showed intact BBB (Fig. 1). The evidence of astrocytic swelling is obvious. We did not observe any significant structural alterations of the brain capillaries of the azoxymethane-induced ALF mice under electron microscopy (Fig. 1a) as compared to the brain of the normal control mice (Fig. 1b). The tight junction was intact. The results from our lab are consistent with the previous

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“…4 A recent study has demonstrated that the addition of peptides corresponding to a portion of the occludin extracellular domain caused increased permeability in cells as measured by TER. 12 This study suggests that disruption of occludin alone is enough to cause a functional change in the tight junctions. In the retina of diabetics, the degradation of occludin by MMPs may therefore disrupt the stability of the tight junction complex between adjacent microvascular endothelial cells leading to leakage and macular edema.…”

Section: Discussionmentioning

confidence: 98%

Matrix metalloproteinases in early diabetic retinopathy and their role in alteration of the blood–retinal barrier

Giebel

Menicucci

McGuire

et al. 2005

Laboratory Investigation

280

232

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One of the early features of diabetic retinopathy is the alteration of the blood-retinal barrier (BRB), which may involve the breakdown of endothelial cell tight junctions. The aim of this study was to examine the expression of extracellular proteinases in an animal model of early diabetic retinopathy and to determine their role in the alteration of the BRB. Matrix metalloproteinase (MMP) expression was studied in the retinas of rats with 12 weeks of diabetes. The role of MMPs in regulating tight junction function was investigated in retinal endothelial and pigment epithelial cells by measuring transepithelial electrical resistance (TER). The retinas of diabetic animals demonstrated elevated levels of MMP-2, MMP-9 and MMP-14 messenger RNA. A significant increase in the production of MMP-9 was seen when cells were exposed to high glucose conditions. Both cell types treated with purified MMP-2 or MMP-9 were found to have alterations of tight junction function as shown by decreased TER. Western blot analysis of cell extracts treated with MMP-2 or MMP-9, revealed specific degradation of the tight junction protein, occludin. Results suggest that elevated expression of MMPs in the retina may facilitate an increase in vascular permeability by a mechanism involving proteolytic degradation of the tight junction protein occludin followed by disruption of the overall tight junction complex.

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A New Principle for Tight Junction Modulation Based on Occludin Peptides

Cited by 105 publications

References 37 publications

Rhinovirus Disrupts the Barrier Function of Polarized Airway Epithelial Cells

Rhinovirus Disrupts the Barrier Function of Polarized Airway Epithelial Cells

Subtle BBB alterations in brain edema associated with acute liver failure

Matrix metalloproteinases in early diabetic retinopathy and their role in alteration of the blood–retinal barrier

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