IL-1β Causes an Increase in Intestinal Epithelial Tight Junction Permeability
Open accessAbstract
IL-1β is a prototypical proinflammatory cytokine that plays a central role in the intestinal inflammation amplification cascade. Recent studies have indicated that a TNF-α- and IFN-γ-induced increase in intestinal epithelial paracellular permeability may be an important mechanism contributing to intestinal inflammation. Despite its central role in promoting intestinal inflammation, the role of IL-1β on intestinal epithelial tight junction (TJ) barrier function remains unclear. The major aims of this study were to determine the effect of IL-1β on intestinal epithelial TJ permeability and to elucidate the mechanisms involved in this process, using a well-established in vitro intestinal epithelial model system consisting of filter-grown Caco-2 intestinal epithelial monolayers. IL-1β (0–100 ng/ml) produced a concentration- and time-dependent decrease in Caco-2 transepithelial resistance. Conversely, IL-1β caused a progressive time-dependent increase in transepithelial permeability to paracellular marker inulin. IL-1β-induced increase in Caco-2 TJ permeability was accompanied by a rapid activation of NF-κB. NF-κB inhibitors, pyrrolidine dithiocarbamate and curcumin, prevented the IL-1β-induced increase in Caco-2 TJ permeability. To further confirm the role of NF-κB in the IL-1β-induced increase in Caco-2 TJ permeability, NF-κB p65 expression was silenced by small interfering RNA transfection. NF-κB p65 depletion completely inhibited the IL-1β-induced increase in Caco-2 TJ permeability. IL-1β did not induce apoptosis in the Caco-2 cell. In conclusion, our findings show for the first time that IL-1β at physiologically relevant concentrations causes an increase in intestinal epithelial TJ permeability. The IL-1β-induced increase in Caco-2 TJ permeability was mediated in part by the activation of NF-κB pathways but not apoptosis.
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Increased serum concentrations of TNF, IL-1β, and IL-6 are potent inducers of intestinal permeability.
“Increased serum concentrations of TNF, IL-1β, and IL-6 have also been shown to be potent inducers of intestinal permeability50–53.”
From Dietary metabolism, the gut microbiome, and heart failure (2019) · cites this paper as [51]
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- Authors
- Al-Sadi, R. M., & Ma, T. Y.
- Affiliations
- Department of Internal Medicine, University of New Mexico School of Medicine , Albuquerque, NM 87131
- University of New Mexico (US)
- ORCID
- Ma, Thomas Y
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2007-04-01
- Volume
- 178
- Issue
- 7
- Pages
- 4641-4649
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- PMC
- PMC3724221
- OpenAlex
- W1618627661
- Cited by
- 601
- References
- 53
- Citations by year
- 2026: 33 · 2025: 32 · 2024: 39 · 2023: 32 · 2022: 47 · 2021: 42 · 2020: 38 · 2019: 38 · 2018: 34 · 2017: 32 · 2016: 28 · 2015: 29 · 2014: 34 · 2013: 31 · 2012: 30
- FWCI
- 18.67
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK064165, R0-1-DK-64165–01)
- Topics
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Keywords
- IL-1β, tight junction permeability, intestinal epithelial barrier, NF-κB activation, Caco-2 cells, intestinal inflammation, paracellular permeability, inulin permeability, pyrrolidine dithiocarbamate, curcumin, NF-κB p65, transepithelial electrical resistance
- MeSH terms
- Curcumin, Humans, Intestinal Mucosa, Membrane Proteins, Permeability, Pyrrolidines, RNA, Messenger, Thiocarbamates, NF-kappa B, Apoptosis, Caco-2 Cells, Tight Junctions, Interleukin-1beta, Occludin
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