CXCR4/SDF-1 Axis Promotes EMT Mediated Fibrosis in Eosinophilic Esophagitis (EoE)
Monday, March 7, 2016
South Exhibit Hall H (Convention Center)
Chandrashekara Puthanapura Mahadevappa, PhD, Sathisha Upparahalli Venkateshaiah, PhD, Murli Manohar, Anil Mishra, PhD FAAAAI
Rationale: Epithelial-Mesenchymal Transition (EMT) is associated with series of events that losses epithelia characteristics and acquire properties of mesenchymal cells, via N-cadherin, and de-polarized cytoskeletal arrangements such as Vimentin.  EMT processes are earlier reported in eosinophilic esophagitis (EoE); however the mechanism of EMT induction in EoE is clearly understood. Herein, we tested the hypothesis that CXCR4/SDF-1 axis may be operational in the induction of EMT in EoE. 

Methods: Accordingly, histological detection of esophageal fibrosis by Masson’s trichrome stain tissue section; pro-inflammatory and pro-fibrotic cytokines levels by performing ELISA and CXCR4/SDF1 and associated signaling molecules by Western Blot analyses. 

Results: DOX induced IL-13 overexpressed mice showed induced SDF-1 and CXCR4 proteins in the esophagus compared to no-DOX exposed mice. Additionally, we observed CXCR4 protein is also induced in vitro in primary esophageal epithelial cells (PEEC) following IL-13 exposure along with TGF-β and TGF-β and N-cadherin levels reduces in IL-13 treated PEEC following the treatment CXCR4 antagonist AMD070. Furthermore, we observed that the levels of mesenchymal marker N-cadherin, TGF-β and Vimentin are induced and epithelial marker E-cadherin is reduced in the esophagus of IL-13 transgenic mice exposed to DOX food compared to no DOX treated mice. Notably IL-13 overexpressed mice show all the characteristics feature of EoE.  

Conclusions: Taken together, we show that CXCR4/SDF-1 axis is involved in EMT process as IL-13 treated primary esophageal epithelial cells and in DOX regulated IL-13 transgenic mice show induced CXC4/SDF1 and CXCR4 antagonist treatment to IL-13 treated PEEC down regulates profibrotic and EMT associated proteins.