ArticleGut2014
In oesophageal squamous cells exposed to acidic bile salt medium, omeprazole inhibits IL-8 expression through effects on nuclear factor-κB and activator protein-1.
Article in Gut, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
39 citing papers in PubMed, 73 citations in OpenAlex.
- Trial
- In Barrett's esophagus patients and Barrett's cell lines, ursodeoxycholic acid increases antioxidant expression and prevents DNA damage by bile acids.American journal of physiology. Gastrointestinal and liver physiology · 2014Trial
- Impact of PAR2 on Tight Junctions and Esophageal Mucosal Inflammation in Rats with Gastroesophageal Reflux Disease.Neurogastroenterology and motility · 2026Article
- Article
- Upper gastrointestinal endoscopy in patients with gastroesophageal reflux disease symptoms: Correlating endoscopic findings with symptoms and pH-impedance results.World journal of gastrointestinal endoscopy · 2026Article
- The oesophagus as an immune organ.Nature reviews. Gastroenterology & hepatology · 2025Review
- Natural Products in the Management of Gastroesophageal Reflux Disease: Mechanisms, Efficacy, and Future Directions.Nutrients · 2025Review
- Review
- Mechanisms of Chinese Medicine in Gastroesophageal Reflux Disease Treatment: Data Mining and Systematic Pharmacology Study.Chinese journal of integrative medicine · 2023Article
- Therapeutic Effect of Polaprezinc on Reflux Esophagitis in the Rat Model.Digestive diseases and sciences · 2023Article
- CCL18 signaling from tumor-associated macrophages activates fibroblasts to adopt a chemoresistance-inducing phenotype.Oncogene · 2023Article
- NF-κB: A novel therapeutic pathway for gastroesophageal reflux disease?World journal of clinical cases · 2022Review
- Roles and action mechanisms of bile acid-induced gastric intestinal metaplasia: a review.Cell death discovery · 2022Review
- Tojapride Reverses Esophageal Epithelial Inflammatory Responses on Reflux Esophagitis Model Rats.Chinese journal of integrative medicine · 2021Article
- Inflammation-Induced Tumorigenesis and Metastasis.International journal of molecular sciences · 2021Review
- Role of microbial dysbiosis in the pathogenesis of esophageal mucosal disease: A paradigm shift from acid to bacteria?World journal of gastroenterology · 2021Review
- Lipid droplet biogenesis and COX-2 pathway activation are triggered by Barrett's esophagus and adenocarcinoma, but not esophageal squamous cell carcinoma risk factors.Scientific reports · 2021Article
- Impact of Deoxycholic Acid on Oesophageal Adenocarcinoma Invasion: Effect on Matrix Metalloproteinases.International journal of molecular sciences · 2020Article
- Associations between the severity of reflux esophagitis in children and changes in oxidative stress, serum inflammation, vasoactive intestinal peptide and motilin.Experimental and therapeutic medicine · 2019Article
- Roles of the hexosamine biosynthetic pathway and pentose phosphate pathway in bile acid-induced cancer development.Cancer science · 2019Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
objectiveOesophagitis might result from the effects of chemokines produced by oesophageal cells in response to gastro-oesophageal reflux, and not solely from the direct, caustic effects of refluxed gastric juice. Proton pump inhibitors (PPI) can block chemokine production through mechanisms independent of their antisecretory effects. We studied omeprazole effects on chemokine production by oesophageal epithelial cells exposed to acidic bile salts.
designHuman primary and telomerase-immortalised oesophageal squamous cells were exposed to acidic bile salt medium with or without omeprazole pretreatment. Interleukin (IL)-8 expression was determined by RT-PCR and ELISA. IL-8 promoter activity was measured by luciferase reporter assay. Binding of NF-κB and AP-1 subunits to the IL-8 promoter was assessed by chromatin immunoprecipitation (ChIP) assay. Immune cell migration induced by conditioned medium was determined by a double-chamber migration assay system.
resultsAcidic bile salt medium caused oesophageal epithelial cells to express IL-8 mRNA and protein by activating the IL-8 promoter through NF-κB and AP-1 binding. Omeprazole inhibited that acidic bile salt-stimulated IL-8 expression by blocking the nuclear translocation of p65 (an NF-κB subunit), and by blocking the binding of p65, c-jun and c-fos (AP-1 subunits) to the IL-8 promoter. Omeprazole also blocked the ability of conditioned medium from cells exposed to acidic bile salts to induce immune cell migration.
conclusionsIn oesophageal squamous epithelial cells, omeprazole inhibits IL-8 expression through effects on NF-κB and AP-1 that are entirely independent of effects on gastric acid secretion. These previously unrecognised PPI effects might contribute to the healing of reflux oesophagitis.
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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.