Tu1124 Evidence for Altered P2X3 Gene Expression Associating With TRPV1 and Neurotrophic Factors in the Inflamed Human Esophagus

Abstract

inflammatory cytokines (IL-8, COX-2, IL-1β, TNF-α, ICAM-1) by RT-PCR. Results: A single, 1-hour exposure to acidic bile salt media significantly increased HRE reporter activity in both NES-G4T (p=0.037) and NES-B10T (p=0.038) cell lines at 24 hours. Following a 10 minute exposure to acidic bile salt media, faint nuclear HIF-1α expression peaked by 2 hours, and decreased by 4 hours in NES-B10T cells. In contrast, nuclear HIF-2α protein increased by 1 hour, and further increased up to 4 hours; this strong and sustained increase in HIF-2α protein expression was confirmed in NES-G4T cells. Exposure to acidic bile salts increased mRNA expression levels of all the HIF-target pro-inflammatory cytokines evaluated in both cell lines. Conclusions: In esophageal squamous cell lines from patients with GERD, exposure to acidic bile salts caused an increase in HIF activity, a strong and sustained increase of HIF-2α nuclear protein, and increased mRNA expression levels of HIF-target pro-inflammatory cytokines. These findings support our hypothesis that exposure to acid and bile salts causes esophageal squamous cells to activate HIF-2α, which causes the secretion of the pro-inflammatory cytokines that mediate reflux esophagitis.