Vitamin D represses rhinovirus replication in cystic fibrosis cells by inducing LL-37

作者：Schogler Aline; Muster Ricardo J; Kieninger Elisabeth; Casaulta Carmen; Tapparel Caroline; Jung Andreas; Moeller Alexander; Geiser Thomas; Regamey Nicolas; Alves Marco P^*

来源：European Respiratory Journal, 2016, 47(2): 520-530.

DOI：10.1183/13993003.00665-2015

Vitamin D has immunomodulatory properties in the defence against pathogens. Its insufficiency is a widespread feature of cystic fibrosis (CF) patients, which are repeatedly suffering from rhinovirus (RV)-induced pulmonary exacerbations.
To investigate whether vitamin D has antiviral activity, primary bronchial epithelial cells from CF children were pre-treated with vitamin D and infected with RV16. Antiviral and anti-inflammatory activity of vitamin D was assessed. RV and LL-37 levels were measured in bronchoalveolar lavage (BAL) of CF children infected with RV.
Vitamin D reduced RV16 load in a dose-dependent manner in CF cells (10(-7) M, p<0.01). The antiviral response mediated by interferons remained unchanged by vitamin D in CF cells. Vitamin D did not exert anti-inflammatory properties in RV-infected CF cells. Vitamin D increased the expression of the antimicrobial peptide LL-37 up to 17.4-fold (p<0.05). Addition of exogenous LL-37 decreased viral replication by 4.4-fold in CF cells (p<0.05). An inverse correlation between viral load and LL-37 levels in CF BAL (r=-0.48, p<0.05) was observed.
RV replication in primary CF bronchial cells was reduced by vitamin D through the induction of LL-37. Clinical studies are needed to determine the importance of an adequate control of vitamin D for prevention of virus-induced pulmonary CF exacerbations.

• 出版日期2016-2