Tumour Necrosis factor-α induces morphological and functional alterations of intestinal HT29 cl.19A cell monolayers

Rodrı́guez, P.; Heyman, Martine; Candalh, Céline; Blaton, Marie-Agnès; Bouchaud, C.

doi:10.1006/cyto.1995.0060

Cited by 99 publications

(71 citation statements)

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“…Several studies have demonstrated that disruption of tight junction is one of important mechanisms involving various models of stimuli-induced epithelial cellular injury. 15,31 We therefore hypothesized that COM crystals might also induce renal tubular epithelial Figure 3 COM crystals induced disruption of tight junction, redistribution and dissociation of occludin and ZO-1. The polarized MDCK cells were incubated with 100 mg/ml COM crystals for 48 h and then processed for double immunofluorescence staining for occludin (in red) and ZO-1 (in green).…”

Section: Discussionmentioning

confidence: 99%

“…Similarly, a large number of previous studies have also reported that disruption of tight junction by oxidants, pathogens and proinflammatory cytokines in various epithelial cells caused declined TER, which was associated with downregulation of occludin and ZO-1. 12,15,21,30,[36][37][38] Our findings indicated that COM crystals caused increased permeability and defective barrier function of tight junction of renal tubular epithelial cells.…”

Section: Zo-1 Occludinmentioning

confidence: 99%

“…10 Tight junction can be disrupted by oxidative stress, [11][12][13] pathogens 14 and proinflammatory cytokines. [15][16][17] A previous study has demonstrated that mutation at C-terminus of occludin leads to increased paracellular permeability and loss of fence function. 18 Occludin is a transmembrane protein that interacts with other tight junction proteins, especially ZO-1, which is the important scaffold protein that links occludin to actin cytoskeleton.…”

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confidence: 99%

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Effects of calcium oxalate monohydrate crystals on expression and function of tight junction of renal tubular epithelial cells

Peerapen

Thongboonkerd

2011

Laboratory Investigation

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Section: Discussionmentioning

confidence: 99%

Section: Zo-1 Occludinmentioning

confidence: 99%

mentioning

confidence: 99%

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Effects of calcium oxalate monohydrate crystals on expression and function of tight junction of renal tubular epithelial cells

Peerapen

Thongboonkerd

2011

Laboratory Investigation

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“…The authors hypothesised that this was due to the appearance of large diameter pores caused by fusion of smaller pores within the tight junction. Interestingly, freeze fracture studies of HT29-cl.19A cell monolayers showed discontinuities in tight junction strands after exposure to mixtures of IFN␥ and tumour necrosis factor-␣ (TNF␣), which was associated with a preferential increase in macromolecular flux (Rodriguez et al, 1995). Similar discontinuities have also been reported in the tight junctions of rat proximal tubule (Orci et al, 1981) and a dual-pathway model has recently been proposed for this tissue involving small tight junction pores (radius 6.7 Å) and infrequent large slit breaks (Guo et al, 2003), which is similar to that derived for colonocyte monolayers using the PEG profiling approach.…”

Section: Discussionmentioning

confidence: 99%

Interferon-γ selectively increases epithelial permeability to large molecules by activating different populations of paracellular pores

Watson

Hoare

Garrod

et al. 2005

Journal of Cell Science

151

109

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Impairment of the gut epithelial barrier by agents such as IFNγ may play a key role in the pathogenesis of inflammatory disorders by increasing the paracellular penetration of luminal macromolecules, potentially including bacterial antigens. Owing to limitations of current paracellular probes, little is known about the precise functional changes induced by IFNγ and how these relate to the development of increased macromolecular permeability. Here we investigate how IFNγ modulates this pathway in T84 monolayers using a novel profiling technique that resolves different populations of paracellular pores by simultaneous analysis of 24 permeability probes of defined molecular size. Two types of functional pore present in control monolayers, an abundant restrictive pore with a radius of ∼4.5 Å and a much larger but infrequent, non-restrictive pore, were differentially regulated by IFNγ. Incubation with IFNγ dose-dependently and reversibly increased the frequency of the non-restrictive pores while having no significant effect on the restrictive component. Cytokine-induced increases in β, the descriptor of the non-restrictive pore, correlated closely with increased permeability to large molecules (10 kDa) including E. coli-derived lipopolysaccharide, but not small (0.182 kDa) molecules. This effect was associated with changes in expression of the tight junction proteins occludin and claudin-1. These data suggest that IFNγ selectively increases the transepithelial flux of large molecules by activating specific pathways within the junctional pore. One hypothesis is that this process may be activated in the early stages of the inflammatory response, facilitating the passage of large and potentially antigenic molecules across the gut without gross disruption of the barrier to small molecules.

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“…The proposed proinflammatory actions of TNF-␣ include production and stimulation of proinflammatory cytokines including IL-1, -6, -8, -12, and granulocyte macrophage colony-stimulating factor, increased expression of endothelial adhesion molecules, activation of acute-phase response, and stimulation of metalloproteinases and collagen synthesis (34,41). In addition to its immune modulating effects, TNF-␣ also caused a disruption of the intestinal epithelial tight junction (TJ) barrier (23,26,33,35). A number of investigators have shown that TNF-␣ produces an increase in intestinal TJ permeability manifested by an increase in paracellular permeability and a drop in transepithelial resistance (TER) (23,26,33,35).…”

mentioning

confidence: 99%

Mechanism of TNF-α modulation of Caco-2 intestinal epithelial tight junction barrier: role of myosin light-chain kinase protein expression

Thomas¹,

Boivin²,

Ye³

et al. 2005

American Journal of Physiology-Gastrointestinal and Liver Physi

411

339

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plays a central role in the intestinal inflammation of various inflammatory disorders including Crohn's disease (CD). TNF-␣-induced increase in intestinal epithelial tight junction (TJ) permeability has been proposed as one of the proinflammatory mechanisms contributing to the intestinal inflammation. The intracellular mechanisms involved in the TNF-␣-induced increase in intestinal TJ permeability remain unclear. The purpose of this study was to investigate the possibility that the TNF-␣-induced increase in intestinal epithelial TJ permeability was regulated by myosin light-chain kinase (MLCK) protein expression, using an in vitro intestinal epithelial model system consisting of the filter-grown Caco-2 intestinal epithelial monolayers. TNF-␣ (10 ng/ml) produced a time-dependent increase in Caco-2 MLCK expression. The TNF-␣ increase in MLCK protein expression paralleled the increase in Caco-2 TJ permeability, and the inhibition of the TNF-␣-induced MLCK expression (by cycloheximide) prevented the increase in Caco-2 TJ permeability, suggesting that MLCK expression may be required for the increase in Caco-2 TJ permeability. The TNF-␣ increase in MLCK protein expression was preceded by an increase in MLCK mRNA expression but not an alteration in MLCK protein degradation. Actinomycin-D prevented the TNF-␣ increase in MLCK mRNA expression and the subsequent increase in MLCK protein expression and Caco-2 TJ permeability, suggesting that the increase in MLCK mRNA transcription led to the increase in MLCK expression. The TNF-␣ increase in MLCK protein expression was also associated with an increase in Caco-2 MLCK activity. The cycloheximide inhibition of MLCK protein expression prevented the TNF-␣ increase in MLCK activity and Caco-2 TJ permeability. Moreover, inhibitors of MLCK, Mg 2ϩ -myosin ATPase, and metabolic energy prevented the TNF-␣ increase in Caco-2 TJ permeability, suggesting that the increase in MLCK activity was required for the TNF-␣-induced opening of the Caco-2 TJ barrier. In conclusion, our results indicate for the first time that 1) the TNF-␣ increase in Caco-2 TJ permeability was mediated by an increase in MLCK protein expression, 2) the increase in MLCK protein expression was regulated by an increase in MLCK mRNA transcription, and 3) the increase in Caco-2 TJ permeability required MLCK protein expression-dependent increase in MLCK activity.

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Tumour Necrosis factor-α induces morphological and functional alterations of intestinal HT29 cl.19A cell monolayers

Cited by 99 publications

References 0 publications

Effects of calcium oxalate monohydrate crystals on expression and function of tight junction of renal tubular epithelial cells

Effects of calcium oxalate monohydrate crystals on expression and function of tight junction of renal tubular epithelial cells

Interferon-γ selectively increases epithelial permeability to large molecules by activating different populations of paracellular pores

Mechanism of TNF-α modulation of Caco-2 intestinal epithelial tight junction barrier: role of myosin light-chain kinase protein expression

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