ArticleThe American journal of pathology2005
Interferon-gamma and tumor necrosis factor-alpha synergize to induce intestinal epithelial barrier dysfunction by up-regulating myosin light chain kinase expression.
Article in The American journal of pathology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 384 papers.
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The trial behind it
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Who cites it
384 citing papers in PubMed, 675 citations in OpenAlex.
- Trial
- Transforming growth factor β-activated kinase 1 as a central integrator of immune-microbiota crosstalk in colitis (Review).Experimental and therapeutic medicine · 2026Review
- The gut-liver axis in drug-induced liver injury (DILI): Interplay between gut microbiota, intestinal barrier, and immune system.Acta pharmaceutica Sinica. B · 2026Review
- Temporal transcriptomic profiling identifies core regulators in cytokine-induced gut barrier disruption in differentiated Caco-2 cells.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Article
- Coffea arabica pulp aqueous extract exhibits the anti-colitogenic effect in mice: preventive efficacy and possible mechanisms of action.Biological research · 2026Article
- Intestinal T cells in aging: implications for gut barrier integrity and inflammaging.GeroScience · 2026Review
- Anaerobe-Driven Inflammation and Epithelial Barrier Disruption in Genital HIV Acquisition.American journal of reproductive immunology (New York, N.Y. : 1989) · 2026Review
- Live tissue microbiota and bacterial translocation: mechanisms and translational perspectives in cardiometabolic diseases.Reviews in endocrine & metabolic disorders · 2026Review
- Betanin ameliorates dextran sulfate sodium-induced colitis in mice by modulating tight junction protein expression.Biochemistry and biophysics reports · 2026Article
- Hydrogen sulfide rescues IFNγ/TNFα-induced intestinal epithelial barrier dysfunction by enhancing oxidative phosphorylation.Scientific reports · 2026Article
- Dietary Antigen Interaction with Intestinal Epithelial Cells.Current allergy and asthma reports · 2026Review
- Pleiotropic effects of all-trans retinoic acid in attenuating the hallmarks of colorectal cancer- challenges and scope of differentiation therapy.Cancer gene therapy · 2026Review
- Tristetraprolin protects against ozone-induced acute lung injury and inflammation in mice.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Inhibition of the T2R/α-Defensin Pathway MediatesToxics · 2026Article
- Article
- Sepsis-associated gastrointestinal dysfunction: neuroimmune mechanisms, gut-brain axis disruption, and therapeutic potential of vagus nerve-targeted neuromodulation.Frontiers in medicine · 2026Review
- The complexity of dementia development and its comorbidities: The collaborative cross-mouse population for multivarious tasks approach.Animal models and experimental medicine · 2026Review
- Dietary Flavonoids as Cross-System Modulators of Hypertension and Intestinal Permeability.Molecules (Basel, Switzerland) · 2025Review
- A Century of Progress Toward Gut Barrier Targeting Therapies in Inflammatory Diseases.The American journal of pathology · 2025Article
- The epithelial barrier theory proposes a comprehensive explanation for the origins of allergic and other chronic noncommunicable diseases.FEBS letters · 2025Review
324 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Numerous intestinal diseases are characterized by immune cell activation and compromised epithelial barrier function. We have shown that cytokine treatment of epithelial monolayers increases myosin II regulatory light chain (MLC) phosphorylation and decreases barrier function and that these are both reversed by MLC kinase (MLCK) inhibition. The aim of this study was to determine the mechanisms by which interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha regulate MLC phosphorylation and disrupt epithelial barrier function. We developed a model in which both cytokines were required for barrier dysfunction. Barrier dysfunction was also induced by TNF-alpha addition to IFN-gamma-primed, but not control, Caco-2 monolayers. TNF-alpha treatment of IFN-gamma-primed monolayers caused increases in both MLCK expression and MLC phosphorylation, suggesting that MLCK is a TNF-alpha-inducible protein. These effects of TNF-alpha were not mediated by nuclear factor-kappaB. However, at doses below those needed for nuclear factor-kappaB inhibition, sulfasalazine was able to prevent TNF-alpha-induced barrier dysfunction, MLCK up-regulation, and MLC phosphorylation. Low-dose sulfasalazine also prevented morphologically evident tight junction disruption induced by TNF-alpha. These data show that IFN-gamma can prime intestinal epithelial monolayers to respond to TNF-alpha by disrupting tight junction morphology and barrier function via MLCK up-regulation and MLC phosphorylation. These TNF-alpha-induced events can be prevented by the clinically relevant drug sulfasalazine.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.