Composition of gastro-oesophageal refluxate.

Gotley, D. C.; Morgan, Anthony; Ball, Daniel; Owen, R. W.; Cooper, M. J.

doi:10.1136/gut.32.10.1093

Cited by 118 publications

(77 citation statements)

References 18 publications

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“…Pepsin is commonly found in the esophagus of patients with GERD (5, 11) and is often detected at high concentrations in patients with stricture or Barrett's esophagus (7). It has been reported that the maximum enzymatic activity of pepsin occurs at pH levels below 3 (41).…”

Section: Discussionmentioning

confidence: 99%

Bile salts disrupt human esophageal squamous epithelial barrier function by modulating tight junction proteins

Chen

Oshima

Shan

et al. 2012

American Journal of Physiology-Gastrointestinal and Liver Physi

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of acid and bile acids contributes to epithelial tissue injury in gastro-esophageal reflux disease. However, the influence of refluxed material on human esophageal stratified epithelial barrier function and tight junction (TJ) proteins has not been fully elucidated. Here, we investigated the influence of acid and bile acids on barrier function and TJ protein distribution using a newly developed air-liquid interface (ALI) in vitro culture model of stratified squamous epithelium based on primary human esophageal epithelial cells (HEECs). Under ALI conditions, HEECs formed distinct epithelial layers on Transwell inserts after 7 days of culture. The epithelial layers formed TJ, and the presence of claudin-1, claudin-4, and occludin were detected by immunofluorescent staining. The NP-40-insoluble fraction of these TJ proteins was significantly higher by day 7 of ALI culture. Exposure of HEECs to pH 2, and taurocholic acid (TCA) and glycocholic acid (GCA) at pH 3, but not pH 4, for 1 h decreased transepithelial electrical resistance (TEER) and increased paracellular permeability. Exposure of cell layers to GCA (pH 3) and TCA (pH 3) for 1 h also markedly reduced the insoluble fractions of claudin-1 and -4. We found that deoxycholic acid (pH 7.4 or 6, 1 h) and pepsin (pH 3, 24 h) significantly decreased TEER and increased permeability. Based on these findings, ALIcultured HEECs represent a new in vitro model of human esophageal stratified epithelium and are suitable for studying esophageal epithelial barrier functions. Using this model, we demonstrated that acid, bile acids, and pepsin disrupt squamous epithelial barrier function partly by modulating TJ proteins. These results provide new insights into understanding the role of TJ proteins in esophagitis. esophageal epithelium; claudin; air-liquid interface THE HUMAN ESOPHAGUS IS LINED with a layer of nonkeratinizing stratified squamous epithelium, which serves as an effective barrier against the influx of luminal contents. The esophageal epithelium consists of the basal, suprabasal, and superficial layers (14). In the pathogenesis of reflux esophagitis, acids, bile acids, and pepsin play a major role in damaging the esophageal epithelium (34). However, the mechanisms by which the luminal contents affect the barrier function of the stratified epithelial cell layers remain unclear.Tight junctions (TJs) separate the apical and basolateral cell surface domains to establish cell polarity and establish barrier function. TJs are composed of several proteins, including occludin, claudins, junctional adhesion molecule (22), and the scaffold protein zonula occludens (ZO). Of these proteins, claudins, which form specialized cellular structures that regulate the permeability of cellular layers, are the most important structural and functional components of TJ strands (1,6,10,30). Claudins are an integral transmembrane protein family consisting of at least 27 subtypes in mammals (22,40) and are essential for establishing and maintaining epithelial cell polarity by controlling the m...

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Section: Discussionmentioning

confidence: 99%

Bile salts disrupt human esophageal squamous epithelial barrier function by modulating tight junction proteins

Chen

Oshima

Shan

et al. 2012

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…[49][50][51] Specific markers of gastric fluid in BAL may prove more sensitive than bile salts as a screening test of aspiration. A small cross sectional study by Ward et al found pepsin, a gastric protease, in the BAL fluid of 13 post-transplant subjects.…”

Section: Effect Of Transplant On Gastro-oesophageal Refluxmentioning

confidence: 99%

Gastro-oesophageal reflux and aspiration in patients with advanced lung disease

Sweet

Patti

Hoopes

et al. 2009

Thorax

123

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“…It is indisputable that acid plays a key role in esophageal mucosal injury, as typical symptoms (heartburn) respond rapidly to antacid ingestion and both symptoms and signs (erosions) of disease are effectively controlled with PPIs or, to a lesser extent, H 2 -receptor antagonists (H2RAs), the principal action of which is to inhibit gastric acid secretion. Pepsin, an acid-activated protease secreted by chief cells in the stomach, is a key component of the refluxate in humans that has been shown experimentally to synergize with acid to produce greater damage to the esophageal epithelium than does exposure to the same concentrations of acid alone [35,36,37,38,39]. Acidified pepsin plays a key role in the development of reflux esophagitis by producing an early irreversible lesion that results in an increase in paracellular permeability, which indirect evidence suggests is due to damage to the junctional complex [21].…”

Section: Role Of Acid and The Possible Mechanisms Involved In Triggermentioning

confidence: 99%

Precise Role of Acid in Non-Erosive Reflux Disease

Wang

Hunt

2008

Digestion

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The fundamental abnormality in gastroesophageal reflux disease is exposure of the esophageal epithelium to acidic gastric contents, resulting in histopathologic injury and/or symptoms. With increasing understanding of gastroesophageal reflux disease, non-erosive reflux disease (NERD) is found to account for >50% of cases involving gastroesophageal reflux. There is a good correlation between esophageal acid exposure (EAE) and endoscopic changes. Duration of EAE correlates with severity of erosive esophagitis (EE), and the number of prolonged acid reflux episodes and esophageal exposure to acid and pepsin is increased in more severe reflux. However, there is no convincing evidence to support a significant difference in the acid secretory capacity between patients with NERD or EE. Although acid reflux gives rise to similar symptoms in both NERD and EE patients, the underlying mechanism of acid injury may be different. Dilated intercellular spaces may be responsible for the enhanced perception of proximal acid reflux and dilated intercellular spaces are a feature of NERD patients, irrespective of EAE, and can be considered an objective, structural marker of reflux symptoms. Three different mechanisms have been proposed to explain the occurrence of heartburn in endoscopy-negative patients: esophageal visceral hypersensitivity, sustained esophageal contractions, and abnormal tissue resistance. Impaired esophageal mucosal resistance or increased sensitivity, even to small amounts of acid reflux, plays a key role in the pathophysiology of NERD. Moreover, hyperalgesia may be a predominant mechanism in eliciting symptoms in NERD patients. Increasingly seen are patients with a poor response to acid suppression treatment. Moreover, even double proton pump inhibitor dosing does not completely inhibit gastric acid secretion and relieve all symptoms. Thus, current definitions of acid reflux require review to increase the sensitivity to determine the frequency and implication of short periods of acidity in the esophagus. Analysis such as analysis of the area under the H⁺ activity time curve is one alternative approach for evaluating acid secretion. The precise role of acid in NERD needs further clarification.

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Composition of gastro-oesophageal refluxate.

Cited by 118 publications

References 18 publications

Bile salts disrupt human esophageal squamous epithelial barrier function by modulating tight junction proteins

Bile salts disrupt human esophageal squamous epithelial barrier function by modulating tight junction proteins

Gastro-oesophageal reflux and aspiration in patients with advanced lung disease

Precise Role of Acid in Non-Erosive Reflux Disease

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