The DOI matches its Crossref record; 31 of the 31 references it cites were found in a registry or an index.
Tumor necrosis factor-alpha (TNFα) regulates the epithelial barrier in the human intestinal cell line HT-29/B6
Abstract
Cytokines are supposed to be mediators in diarrhoeal diseases. The aim of this study is to characterize the effect of tumor necrosis factor-alpha (TNFα) on epithelial barrier function in the colonic epithelial cell line HT-29/B6. Active ion transport and barrier function were measured as short-circuit current and transepithelial electrical resistance (Rt), respectively. In parallel, freeze-fracture electron microscopy (EM) of tight junctions (TJ) and immunofluorescence microscopy of the zonula occludens protein-1 (ZO-1) were performed. Serosal addition of TNFα (100 ng/ml) decreased Rt by 81%. This effect was dose-dependent and could be mimicked by antibodies against the p55 form of the TNF receptor. Cytotoxic effects were excluded by a negative lactate dehydrogenase (LDH) assay. Immunofluorescence localization with anti-ZO-1 antibodies revealed no evidence for disruption of the monolayer after TNFα treatment. In freeze-fracture EM, TJ complexity was decreased by TNFα, as indicated by a decrease in the number of strands from 4.7 to 3.4. The tyrosine kinase blocker genistein and the protein kinase A inhibitor H-8 reduced the effect of TNFα. A combination of TNFα with interferon-γ acted synergistically on the epithelial barrier. In conclusion, TNFα impairs epithelial barrier function by altering structure and function of the tight junction, which could be of pathogenic relevance in intestinal inflammation.
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Cites
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Cited by
Regulation of Tight Junction Permeability by Intestinal Bacteria and Dietary Components1,2
Ulluwishewa, D., Anderson, R. C., McNabb, W. C., Moughan, P. J., Wells, J. M., & Roy, N. C. (2011) · The Journal of Nutrition · doi:10.3945/jn.110.135657 · Cited by 1,177
Gut-liver axis: Pathophysiological concepts and clinical implications
Tilg, H., Adolph, T. E., & Trauner, M. (2022) · Cell Metabolism · doi:10.1016/j.cmet.2022.09.017 · Cited by 843
Michielan, A., & D’Incà, R. (2015) · Mediators of Inflammation · doi:10.1155/2015/628157 · Cited by 709
Inflammatory processes have differential effects on claudins 2, 3 and 4 in colonic epithelial cells
Prasad, S., Mingrino, R., Kaukinen, K., Hayes, K. L., Powell, R. M., MacDonald, T. T., & Collins, J. E. (2005) · Laboratory Investigation · doi:10.1038/labinvest.3700316 · Cited by 490
Ma, T. Y., Boivin, M. A., Ye, D., Pedram, A., & Said, H. M. (2005) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00412.2004 · Cited by 452
Metadata
- Authors
- Schmitz, H., Fromm, M., Bentzel, C. J., Scholz, P., Detjen, K., Mankertz, J., Bode, H., Epple, H.-J., Riecken, E.-O., & Schulzke, J.-D.
- Venue
- Journal of Cell Science
- Publisher
- The Company of Biologists
- Published
- 1999-01-01
- Volume
- 112
- Issue
- 1
- Pages
- 137-146
- ISSN
- 0021-9533 (ISSN-L)
- 1477-9137
- OpenAlex
- W2110174748
- Cited by
- 375
- References
- 31
- FWCI
- 8.44
- Type
- journal article
- Language
- en
- Open access
- closed
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- Schmitz, H., Fromm, M., Bentzel, C. J., Scholz, P., Detjen, K., Mankertz, J., Bode, H., Epple, H.-J., Riecken, E.-O., & Schulzke, J.-D. (1999). Tumor necrosis factor-alpha (TNFα) regulates the epithelial barrier in the human intestinal cell line HT-29/B6. Journal of Cell Science. https://doi.org/10.1242/jcs.112.1.137
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