Differential Treatment effects of Budesonide on Eosinophilic Esophagitis (EoE) versus Healthy Fibroblasts.
Sunday, March 4, 2018
South Hall A2 (Convention Center)
Lance Y. Hsieh
RATIONALE: Topical esophageal corticosteroid therapy reduces eosinophilic inflammation in esophageal epithelium in EoE. TCS can also diminish subepithelial fibrosis pediatric EoE subjects who respond to therapy. However, whether topical steroids direct alter esophageal fibroblast function and whether there are differential effects on normal versus EoE fibroblasts is unclear.

METHODS: Esophageal fibroblasts from 3 children with active EoE (2 non-responders to budesonide, 1 on proton pump inhibitor monotherapy) and 2 healthy donors were isolated and cultured from the esophagus. EoE and normal fibroblasts were matched for culture conditions and passage and treated concurrently. Fibroblasts were treated with TGFb1 (1ng/ml) in the presence or absence of budesonide (0.01uM) and qPCR was performed to analyze gene expression of fibrotic genes.

RESULTS: Both EoE and normal fibroblasts had significant increases in remodeling gene expression with TGFb1 treatment (collagen, fibronectin, PLN, PAI-1, and aSMA p<0.01 for all). Both EoE and normal fibroblasts had significant decreases in TGFb1-induced collagen and PLN (p<0.01) in the presence of budesonide but only normal fibroblasts had a significant reduction in TGFb1 induced aSMA (p<0.001). Compared with normal fibroblasts, EoE fibroblasts had significantly less down regulation of TGFb1-induced fibronectin, aSMA, PLN, and PAI-1 expression in the presence of budesonide (p<0.01 for all).

CONCLUSIONS: Budesonide was less effective at inhibiting fibrotic genes expression in EoE as opposed to normal fibroblasts. This may reflect intrinsic differences in esophageal fibroblasts from diseased versus normal subjects and may have therapeutic implications in EoE.