EPs^? 7630 Stimulates Tissue Repair Mechanisms and Modifies Tight Junction Protein Expression in Human Airway Epithelial Cells

Airway epithelium repair after infection consists of wound repair, re-synthesis of the extracellular matrix (ECM), and tight junction proteins. In humans, EPs((R)) 7630 obtained from Pelargonium sidoides roots reduces the severity and duration of acute respiratory tract infections. The effect of EPs((R)) 7630 on tissue repair of rhinovirus-16 (RV-16) infected and control human airway epithelial cells was assessed for: (i) epithelial cell proliferation by manual cell counts, (ii) epithelial wound repair by "scratch assay", (iii) ECM composition by Western-blotting and cell-based ELISA, and (iv) epithelial tight junction proteins by Western-blotting. EPs((R)) 7630 stimulated cell proliferation through cAMP, CREB, and p38 MAPK. EPs((R)) 7630 significantly improved wound repair. Pro-inflammatory collagen type-I expression was reduced by EPs((R)) 7630, while fibronectin was increased. Virus-binding tight junction proteins desmoglein2, desmocollin2, ZO-1, claudin1, and claudin4 were downregulated by EPs((R)) 7630. The RV16-induced shift of the ECM towards the pro-inflammatory type was prevented by EPs((R)) 7630. Most of the effects of EPs((R)) 7630 on tissue repair and regeneration were sensitive to inhibition of cAMP-induced signaling. The data suggest that EPs((R)) 7630-dependent modification of epithelial cell metabolism and function might underlie the faster recovery time from viral infections, as reported by others in clinical studies.