ArticlePloS one2014
Interleukin-6 modulation of intestinal epithelial tight junction permeability is mediated by JNK pathway activation of claudin-2 gene.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 155 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
155 citing papers in PubMed, 257 citations in OpenAlex.
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- Increased Plasma Levels of Gut-Derived Phenolics Linked to Walking and Running Following Two Weeks of Flavonoid Supplementation.Nutrients · 2018Trial
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- The gut-lung axis in early life: microbiome-associated mechanisms and clinical relevance.European respiratory review : an official journal of the European Respiratory Society · 2026Review
- Pro-Inflammatory Cytokines as Core Mediators of Colonic Epithelial Barrier Dysfunction: Roles of TNF-α, IFN-γ, IL-1β, and IL-6.International journal of molecular sciences · 2026Review
- Ezetimibe Normalizes Dietary Cholesterol-Induced Exacerbation of Liver Injury in Alcohol-Fed Mice.Biomolecules · 2026Article
- The Gut Microbiota-Mast Cell Axis in Intestinal Homeostasis and Food Allergy Pathogenesis.Biomolecules · 2026Review
- Tristetraprolin protects against ozone-induced acute lung injury and inflammation in mice.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Plant-derived betaine enhances barrier integrity and immune responses in canine intestinal epithelial cells and macrophages under endotoxin challenge.Journal of animal science · 2026Article
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- Serum TNF-α as an indicator reflecting the severity of intestinal barrier injury in a neonatal rat model of necrotizing enterocolitis.Frontiers in pediatrics · 2026Article
- Anti-Inflammatory Properties of Ripe and Unripe Papaya Pectin in a Neonatal Human Stem Cell-Derived Ileum Model.Molecular nutrition & food research · 2026Article
- Sepsis-associated gastrointestinal dysfunction: neuroimmune mechanisms, gut-brain axis disruption, and therapeutic potential of vagus nerve-targeted neuromodulation.Frontiers in medicine · 2026Review
- Gut-Brain Axis and Perioperative Gut Microbiome in Postoperative Cognitive Dysfunction: Implications for Neurosurgical Patients.Medical sciences (Basel, Switzerland) · 2025Review
- Assessment of intestinal barrier integrity and associations with innate immune activation and metabolic syndrome in acutely ill, antipsychotic-free schizophrenia patients.Journal of neuroinflammation · 2025Article
- Low-dose rituximab in lupus enteritis: a comparative study on its efficacy in modulating mucosal immunity and reducing inflammation.Arthritis research & therapy · 2025Article
- Neuroimmune, metabolic and oxidative stress pathways in major depressive disorder.Nature reviews. Neurology · 2025Review
- Role of C-Jun N-Terminal Kinases on a Stressed Epithelium: Time for Testing Isoform Specificity.Biology · 2025Review
- Dysregulation of immune system markers, gut microbiota and short-chain fatty acid production following prenatal alcohol exposure: A developmental perspective.Neurochemistry international · 2025Article
95 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
7 authors at 2 institutions in 1 country.
Funding
Abstract
Defective intestinal epithelial tight junction (TJ) barrier has been shown to be a pathogenic factor in the development of intestinal inflammation. Interleukin-6 (IL-6) is a pleiotropic, pro-inflammatory cytokine which plays an important role in promoting inflammatory response in the gut and in the systemic circulation. Despite its key role in mediating variety inflammatory response, the effect of IL-6 on intestinal epithelial barrier remains unclear. The purpose of this study was to investigate the effect of IL-6 on intestinal epithelial TJ barrier and to delineate the intracellular mechanisms involved using in-vitro (filter-grown Caco-2 monolayers) and in-vivo model (mouse intestinal perfusion) systems. Our results indicated that IL-6 causes a site-selective increase in Caco-2 intestinal epithelia TJ permeability, causing an increase in flux of small-sized molecules having molecular radius <4 Å. The size-selective increase in Caco-2 TJ permeability was regulated by protein-specific increase in claudin-2 expression. The IL-6 increase in TJ permeability required activation of JNK signaling cascade. The JNK pathway activation of AP-1 resulted in AP-1 binding to its binding sequence on the claudin-2 promoter region, leading to promoter activation and subsequent increase in claudin-2 gene transcription and protein synthesis and TJ permeability. Our in-vivo mouse perfusion showed that IL-6 modulation of mouse intestinal permeability was also mediated by AP-1 dependent increase in claudin-2 expression. In conclusion, our studies show for the first time that the IL-6 modulation of intestinal TJ permeability was regulated by JNK activation of AP-1 and AP-1 activation of claudin-2 gene.
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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.