Leaks in the epithelial barrier caused by spontaneous and TNF‐α‐induced single‐cell apoptosis
Abstract
Current opinion assumes epithelial integrity during spontaneous apoptotic cell death. We measured, for the first time, the local conductances associated with apoptoses and show leaks of up to 280 nS (mean 48 +/- 19 nS) in human intestinal epithelium. The results disprove the dogma that isolated cell apoptosis occurs without affecting the epithelial cell permeability barrier. After induction by tumor necrosis factor alpha (TNF-alpha) the apoptotic leaks were dramatically enhanced: not only was the frequency increased by threefold, but the mean conductance also increased by 12-fold (597+/-98 nS). Thus, apoptosis accounted for about half (56%) of the TNF-alpha-induced permeability increase whereas the other half was caused by degradation of tight junctions in nonapoptotic areas. Hence, spontaneous and induced apoptosis hollow out the intestinal barrier and may facilitate loss of solutes and uptake of noxious agents.
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TNF-α induced loss of epithelial integrity due to apoptosis accounted for about 56% of the damage, and the rest was by disruption of tight junctions in nonapoptotic areas.
“TNF-α induced loss of the epithelial integrity due to apoptosis accounted for about 56% of the damage and the rest was by disruption of TJs in nonapoptotic areas.57”
From Regulation of Intestinal Barrier Function by Microbial Metabolites (2021) · cites this paper as [57]
TNF-α disrupts the gut barrier not only by degradation in tight junctions, but also through the induction of epithelial apoptosis.
“For example, Gitter et al57 showed that tumor necrosis factor alpha (TNF-α) disrupts the gut barrier not only by degradation in TJs, but also through the induction of epithelial apoptosis.”
From Regulation of Intestinal Barrier Function by Microbial Metabolites (2021) · cites this paper as [57]
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References 36 · Cited by 250
- Authors
- Gitter, A. H., Bendfeldt, K., Schulzke, J.-D., & Fromm, M.
- Affiliations
- Freie Universität Berlin (DE)
- Corresponding author
- Gitter, Alfred H.
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 2000-09
- Volume
- 14
- Issue
- 12
- Pages
- 1749-1753
- ISSN
- 0892-6638 (ISSN-L)
- 1530-6860
- OpenAlex
- W2078519703
- Cited by
- 250
- References
- 36
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 4 · 2023: 4 · 2022: 8 · 2021: 12 · 2020: 8 · 2019: 5 · 2018: 8 · 2017: 12 · 2016: 8 · 2015: 12 · 2014: 7 · 2013: 7 · 2012: 18
- FWCI
- 2.17
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The FASEB Journal (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion Transport and Channel Regulation
- Keywords
- epithelial permeability, apoptosis, TNF-α, intestinal epithelium, tight junctions, barrier integrity, intestinal permeability
- MeSH terms
- Electric Conductivity, Electrophysiology, Epithelial Cells, Humans, Intestinal Mucosa, Permeability, Tumor Necrosis Factor-alpha, Apoptosis, HT29 Cells, Tight Junctions
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