Expression of Adhesion Molecules in a Gastroduodenal Reflux Murine Model
Abstract
BACKGROUND
Various adhesion molecules including intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) have been shown to play a role in inflammation as well as contribute to tumor progression and prognosis. We hypothesized that gastroduodenal reflux upregulates ICAM-1 and VCAM-1 expression in the distal esophagus, serving as possible early markers of pathologic esophageal disease.
METHODS
Normal human esophageal epithelial cells (HET1A), Barrett's cells (CPB), and esophageal adenocarcinoma cells (FLO1 and OE33) were treated with deoxycholic acid (DCA) at increasing concentrations for 24 hours. Adhesion molecule expression was assessed using immunoblotting. A surgical mouse reflux model was generated by performing a side-to-side anastomosis between the gastroesophageal junction and the first portion of the duodenum (duodeno-gastroesophageal anastomosis, DGEA). Esophageal sections were evaluated using H&E staining, immunohistochemistry, and immunofluorescence.
RESULTS
DCA induced a significant increase in ICAM-1 and VCAM-1 expression in HET1A, CPB, FLO1, and OE33 cells. Animals undergoing DGEA demonstrated a significant increase in mucosal hyperplasia (p<0.0001) and cellular proliferation (p<0.0001) compared to control animals. Immunofluorescence and western blot analysis of the lower esophagus demonstrated significant upregulation of ICAM-1 (p=0.005), with no change in VCAM-1 expression (p=0.82).
CONCLUSIONS
Our results reveal that ICAM-1…
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