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- W2000763281 abstract "TNF-α is a widely distributed proinflammatory cytokine, involved in many disease states. Although it has widely distributed effects, a precise mechanism of action has never been described, in particular at the epithelial level. Morpho-functional changes of the intestinal epithelial monolayer HT29 cl.19A exposed to TNF-α were therefore assessed, using electron microscopy (including freeze-fracture replica analysis), as well as measurement of mannitol, Na+and horseradish peroxidase fluxes across intestinal HT29 cl.19A cell monolayers using Ussing chambers. TNF-α receptors were induced on HT29 cl.19A cells by a small non-toxic dose of IFN-γ (5 U/ml). After 4 h of the combined presence of TNF-α (10 ng/ml) and IFN-γ (5U/ml), the tight junction structure was altered as shown by a significant decrease in the average strand number measured in the apico-basal direction (5.50±2.70 vs 3.73±1.39 in control and treated cells respectively,P<0.0001) and by a significant decrease in junctional depth (0.27±0.14 and 0.17±0.10 μm in control and treated cells respectively,P<0.0001). These results are in agreement with a decrease in number of ‘kiss’ sites between contiguous membranes of TNF-α treated cells observed in ultrathin sections. In parallel, the paracellular permeability of intestinal monolayers increased in the presence of TNF-α compared to controls as shown by the increase in mannitol ( 32.4±4.7 vs 9.3±0.7 μg/h.cm2,P<0.0003), Na (216±27 vs 83±4 μg/h.cm2,P<0.0003) and HRP (274±67 vs 34±12 ng/h.cm2,P<0.004) fluxes and by the decrease in electrical resistance (43±7 vs 112±10 Ω.cm2,P<0.0001). These results indicate that, providing receptors are present, TNF-α induces an alteration of epithelial tight junctions leading to a disruption of the epithelial barrier capacity." @default.
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- W2000763281 date "1995-07-01" @default.
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- W2000763281 title "Tumour Necrosis factor-α induces morphological and functional alterations of intestinal HT29 cl.19A cell monolayers" @default.
- W2000763281 doi "https://doi.org/10.1006/cyto.1995.0060" @default.
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