Novel regulators of airway epithelial barrier function during inflammation: potential targets for drug repurposing

IL-4 and IL-13 signaling are the major pathways disrupting the airway epithelial barrier during airway inflammation. However, blocking IL-4/IL-13 signaling may adversely affect protective immune responses and increase susceptibility of host to infections. An alternate approach to modulate airway epithelial barrier function involves therapeutically targeting specific downstream component of IL-4/IL-13 signaling or different inflammatory mediators responsible for regulation of airway epithelial barrier. Airway epithelium-targeted therapy using inhibitors of HDAC, HSP90, MIF, mTOR, IL-17A and VEGF may be a potential strategy to prevent airway epithelial barrier dysfunction in airway inflammatory diseases.