Alterations in junctional proteins, inflammatory mediators and extracellular matrix molecules in eosinophilic esophagitis

- We examined alterations in cell junctions and inflammatory mediators in EoE.
- E-cadherin and claudin-1 expression was reduced; occludin expression was increased.
- Vimentin expression was increased, multiple reactive bands indicating fragmentation.
- IL-1α and IL-1Ra protein expression was reduced; EGF expression was increased.
- We identified novel factors likely involved in epithelial barrier disruption in EoE.

Eosinophilic esophagitis (EoE), an inflammatory atopic disease of the esophagus, causes massive eosinophil infiltration, basal cell hyperplasia, and sub-epithelial fibrosis. To elucidate cellular and molecular factors involved in esophageal tissue damage and remodeling, we examined pinch biopsies from EoE and normal pediatric patients. An inflammation gene array confirmed that eotaxin-3, its receptor CCR3 and interleukins IL-13 and IL-5 were upregulated. An extracellular matrix (ECM) gene array revealed upregulation of CD44 & CD54, and of ECM proteases (ADAMTS1 & MMP14). A cytokine antibody array showed a marked decrease in IL-1α and IL-1 receptor antagonist and an increase in eotaxin-2 and epidermal growth factor. Western analysis indicated reduced expression of intercellular junction proteins, E-cadherin and claudin-1 and increased expression of occludin and vimentin. We have identified a number of novel genes and proteins whose expression is altered in EoE. These findings provide new insights into the molecular mechanisms of the disease.