ArticleThe American journal of pathology2013
TNF-α modulation of intestinal epithelial tight junction barrier is regulated by ERK1/2 activation of Elk-1.
Article in The American journal of pathology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 134 papers.
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Who cites it
134 citing papers in PubMed, 251 citations in OpenAlex.
- Ancient grain flour consumption as a novel therapeutic approach for irritable bowel syndrome.European journal of nutrition · 2025Trial
- Recurrent Severe Subclinical Mastitis and the Risk of HIV Transmission Through Breastfeeding.Frontiers in immunology · 2022Trial
- Gut microbiota shifts in spaceflight: a case study evidence and countermeasures for microbial homeostasis.3 Biotech · 2026Review
- Artificial and natural non-nutritive sweeteners drive divergent gut and genetic responses across generations.Frontiers in nutrition · 2026Article
- The gut-heart axis in heart failure: from bidirectional pathophysiological mechanisms to integrative therapeutic strategies.Frontiers in microbiology · 2026Review
- The non-synthetic sweeteners, miraculin and mogroside V, but not stevia, disrupt the intestinal epithelial barrier function through a sweet taste receptor-dependent mechanism.Scientific reports · 2025Article
- Dietary Flavonoids as Cross-System Modulators of Hypertension and Intestinal Permeability.Molecules (Basel, Switzerland) · 2025Review
- Chlorogenic acid reduces Lipopolysaccharide-Induced intestinal inflammation through Inhibition of acetylcholinesterase and activation of muscarinic receptors.Molecular biology reports · 2025Article
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- 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
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- The Role of TNF-α in Neuropathic Pain: An Immunotherapeutic Perspective.Life (Basel, Switzerland) · 2025Review
- Influence of Saccharomyces cerevisiae CNCM I-1077 on the fecal pH, markers of gut permeability, fecal microbiota, and markers of systemic inflammation in sedentary horses fed a high-starch diet.Journal of animal science · 2025Article
- Modulation of pulmonary immune functions by theFrontiers in immunology · 2025Review
- Neisseria gonorrhoeae induces local secretion of IL-10 at the human cervix to promote colonization.The Journal of clinical investigation · 2024Article
- Eimeria: Navigating complex intestinal ecosystems.PLoS pathogens · 2024Review
- Glucoraphanin and sulforaphane mitigate TNFα-induced Caco-2 monolayers permeabilization and inflammation.Redox biology · 2024Article
- Cystathionine Gamma-Lyase Regulates TNF-α-Mediated Injury Response in Human Colonic Epithelial Cells and Colonoids.Antioxidants (Basel, Switzerland) · 2024Article
74 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Tumor necrosis factor (TNF-α) is a proinflammatory cytokine that plays a critical role in the pathogenesis of inflammatory bowel disease. TNF-α causes an increase in intestinal permeability; however, the signaling pathways and the molecular mechanisms involved remain unclear. The major purpose of this study was to investigate the role of MAP kinase pathways (ERK1/2 and p38 kinase) and the molecular processes involved. An in vitro intestinal epithelial model system consisting of Caco-2 monolayers and an in vivo mouse model system were used to delineate the cellular and molecular mechanisms involved in TNF-α effects on tight junction barrier. The TNF-α-induced increase in Caco-2 tight junction permeability was mediated by activation of the ERK1/2 signaling pathway, but not the p38 kinase pathway. Activation of the ERK1/2 pathway led to phosphorylation and activation of the ETS domain-containing transcription factor Elk-1. The activated Elk-1 translocated to the nucleus, where it bound to its binding motif on the myosin light chain kinase (MLCK) promoter region, leading to the activation of MLCK promoter activity and gene transcription. In addition, in vivo intestinal perfusion studies also indicated that the TNF-α-induced increase in mouse intestinal permeability requires ERK1/2-dependent activation of Elk-1. These studies provide novel insight into the cellular and molecular processes that regulate the TNF-α-induced increase in intestinal epithelial tight junction permeability.
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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.