Up-Regulated Vitamin D Receptor by Extract EPs 7630 Contributes to Rhinovirus Defense in Bronchial Epithelial Cells

EPs7630, extracted from , reduces the severity of viral upper respiratory tract infections. Vitamin D also improves anti-viral host defense through similar signaling pathways. This study assessed if EPs7630 modifies vitamin D receptor (VDR) expression and function by human bronchial epithelial cells. Bronchial epithelial cells were incubated with EPs7630 over 48 h before calcitriol stimulation and/or infection with (RV)-16. Protein expression was determined by Western-blotting. Intracellular signaling of mitogen activated protein kinases (MAPK) was studied by chemical inhibitors. The anti-viral effect was assessed by immunofluorescence for RV-16 protein. EPs7630 upregulated VDR expression through Erk1/2 MAPK and thereby increased the cell's sensitivity to calcitriol. Compared ton untreated cells, the shift of the VDR into the nucleus at 5.3 times lower calcitriol concentration. EPs7630 increased Erk1/2 MAPK signaling, but reduced p38 phosphorylation, and had no effect on Jun N-terminal kinase (JNK). EPs7630 improved the anti-viral effect of vitamin D on RV-16 infection by 2.1 folds compared to vitamin D alone or to untreated cells. Furthermore, EPs7630 improved the differentiation of epithelial cells by upregulating E-cadherin expression through Erk1/2. In conclusion, EPs7630 increased host defense against infection by upregulating the VDR and the differentiation of epithelial cells.