Rationale: Inward rectifying potassium channel KCNJ2 is upregulated in the epithelium of eosinophilic esophagitis (EoE) patients compared to healthy controls. However, whether KCNJ2 contributes to GI Th2 inflammation and epithelium barrier impairment in EoE is unknown.
Methods: We employed the EPC2 human
Results: Following IL-13 stimulation, KCNJ2 overexpression increases CCL26 (eotaxin-3) production by 3.2 fold compared to empty vector (EV) controls (P<0.05). Additionally, KCNJ2 overexpression increases the IL-13 induced barrier impairment by 45% compared to EV controls (P<0.05). With a Poly I:C stimulation, KCNJ2 overexpressing EPC2 cells produce 15-fold more TSLP mRNA and 3.4-fold more protein compared to EV controls (P<0.001). Likewise, KCNJ2 overexpressing cells produced increased mRNA for IL-8 (6-fold, P<0.01), GM-CSF (14-fold, P<0.01) and IFN-β (6-fold, P<0.01). Finally, KCNJ2 overexpressing cells produced 23-fold higher CCL26 mRNA compared with unstimulated controls following exposure to Aspergillus fumigatus extract (50ug/mL, 24 hours) in contrast to
Conclusions: KCNJ2 overexpression is sufficient to induce pro-EoE like changes in
Full conference title:
- AAAAI 2017 (73rd)