Weak acids induce PGE2 production in human oesophageal cells: novel mechanisms underlying GERD symptoms.

The role of weak acids with pH values in the range of 4-7 has been implicated in the symptoms of gastroesophageal reflux disease (GERD). Prostaglandin E2 (PGE2) is associated with heartburn symptom in GERD patients; however, the precise productive mechanisms remain unclear. In this study, we revealed that exposure to weak acids increases PGE2 production with a peak at pH 4-5, slightly in human normal oesophageal cells (Het-1A), and robustly in oesophageal squamous carcinoma cells (KYSE-270). Release of PGE2 from the oesophageal mucosa was augmented by weak acid treatment in rat. Chenodeoxycholic acid (CDCA), a bile acid, upregulated cyclooxygenase-2 (COX-2) expression in Het-1A and KYSE-270 and induced PGE2 production in KYSE-270 cells. Weak acid-induced PGE2 production was significantly inhibited by cytosolic phospholipase A2 (cPLA2), ERK, and transient receptor potential cation channel subfamily V member 4 (TRPV4), a pH-sensing ion channel, inhibitors. Hangeshashinto, a potent inhibitor of COX-2, strongly decreased weak acid- and CDCA-induced PGE2 levels in KYSE-270. These results indicated that weak acids induce PGE2 production via TRPV4/ERK/cPLA2 in oesophageal epithelial cells, suggesting a role in GERD symptoms like heartburn. Interventions targeting pH values up to 5 may be necessary for the treatment of GERD.

Germination of pollen grains in the oesophagus of individuals with eosinophilic oesophagitis.

BACKGROUND: Eosinophilic oesophagitis (EoE) is characterized by oesophageal dysfunction and, histologically, by eosinophilic inflammation. There is no a clear aetiologic treatment. EoE exacerbations are often seasonal. We hypothesized that the inflammatory response of the oesophageal mucosa in patients with high levels of antibodies to pollen allergens and worsened seasonal EoE might be due to swallowing airborne pollen and the intrusion into the oesophageal mucosa of pollen allergens and pollen tubes, which encounter a pH and humidity resembling the stigma at pollination. OBJECTIVE: The aim of our study was to demonstrate the possible pathogenic role of environmental allergens in EoE through molecular and anatomopathological studies METHODS: One hundred and twenty-nine patients with EoE were tested for environmental and food allergens. Component resolved diagnosis (CRD), histological and botanical analysis was performed. Microscopic examination of oesophageal biopsies of 129 adults patients with EoE, 82 of them with seasonal exacerbation, and 100 controls, with gastroesophageal reflux without eosinophilic infiltrate, were made to verify the presence of callose (polysaccharide abundant in pollen tubes but absent in animal tissues) in the oesophagus. RESULTS: Component resolved diagnosis detected pollen allergens in 87.6% of patients with EoE. The predominant allergens were group 1 grass (55%), Art v 3 (11.3%) and lipid transfer proteins (LTPs) (19.4%) of common Mediterranean foods such as peach, hazelnuts, walnuts and wheat. Callose from pollen tubes was found in 65.6% of biopsies. CONCLUSION: Alteration of the mucosal barrier in EoE might cause the penetration of pollen grains into the oesophageal tissues. In EoE patients, anatomopathological studies searching for intrusion to plant foods and pollen, and specific-guided diet and immunotherapy after plant structures detection in biopsies, might be effective. CLINICAL RELEVANCE: It is possible to see the intrusion into animal tissues (oesophagus mucosa) of plant structures (pollen grains or pollen tubes) using an adecuate histologic botanical analysis. Molecular and anatomopathological studies can help to demonstrate a possible pathogenic role of environmental allergens in EoE.

Anti-apoptotic effect of banhasasim-tang on chronic acid reflux esophagitis.

AIM: To evaluate the anti-apoptotic effect of banhasasim-tang (BHSST) on chronic acid reflux esophagitis (CARE) using a rat model. METHODS: A surgically-induced CARE model was established in Sprague-Dawley rats. The modeled rats were divided into a treatment group or untreated group, and given BHSST (1 g/kg body weight per day) or water, respectively, for 15 consecutive days (n = 7 each group). Changes in expression of proteins related to nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and apoptosis were assessed by western blotting. Changes in esophageal pathology were analyzed by gross and histological examinations. RESULTS: The CARE exposure modeled rats showed increased levels of the NADPH oxidase subunit, NOX4 and p47phox in the esophagus. The BHSST treatment completely resolved these CARE-related increases. The CARE rats also showed markers of cytokine stress, including elevated levels of TNF-α and reactive oxygen species as well as of the consequent increase in JNK activation, and subsequent decrease in pro-survival gene expression, such as of Bcl-2. BHSST treatment resolved the CARE-related changes. BHSST also exerted an anti-apoptotic effect, as evidenced by altered expression of the apoptosis-related genes for bax, cytochrome c, and caspase 3. Finally, the BHSST treatment markedly ameliorated the CARE-related esophageal mucosal ulcerations. CONCLUSION: In the rat model of CARE, BHSST can suppress development of esophageal mucosal ulceration via regulation of reactive oxygen species-dependent apoptosis.