Up‐regulated vitamin d receptor by pelargonium sidoides extract eps® 7630 contributes to rhinovirus defense in bronchial epithelial cells

Abstract

EPs®7630, extracted from Pelargonium sidoides, 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 EPs® 7630 modifies vitamin D receptor (VDR) expression and function by human bronchial epithelial cells. Bronchial epithelial cells were incubated with EPs® 7630 over 48 h before calcitriol stimulation and/or infection with Rhinovirus (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. EPs® 7630 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. EPs® 7630 increased Erk1/2 MAPK signaling, but reduced p38 phosphorylation, and had no effect on Jun N‐terminal kinase (JNK). EPs® 7630 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, EPs® 7630 improved the differentiation of epithelial cells by upregulating E‐cadherin expression through Erk1/2. In conclusion, EPs® 7630 increased host defense against Rhinovirus infection by upregulating the VDR and the differentiation of epithelial cells.