ABSTRACT
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(-7â )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.
Subject(s)
Cathelicidins/drug effects , Cholecalciferol/pharmacology , Cystic Fibrosis/metabolism , Epithelial Cells/drug effects , Rhinovirus/drug effects , Virus Replication/drug effects , Vitamins/pharmacology , Adolescent , Antimicrobial Cationic Peptides , Bronchi/cytology , Bronchoalveolar Lavage Fluid/chemistry , Bronchoalveolar Lavage Fluid/virology , Case-Control Studies , Cathelicidins/metabolism , Child , Child, Preschool , Cystic Fibrosis/virology , Epithelial Cells/virology , Female , Humans , Infant , Male , Real-Time Polymerase Chain Reaction , Viral Load , Vitamin D/pharmacologyABSTRACT
Bactericidal activities of neutrophils occur by two distinctive mechanisms that are oxygen-dependent and -independent. Human cathelicidin antimicrobial peptide 18 (hCAP18), also known as LL-37/FALL-39, is a neutrophil-specific granule protein. We compared the content of hCAP18 and neutrophil gelatinase-associated lipocalin (NGAL), another neutrophil-specific granule protein, in neutrophils of both neonates and adults by flow cytometry. The percentage as well as fluorescence intensity ratio of hCAP18 and NGAL expression in neonate neutrophils were significantly lower than in adults. Expression of hCAP18 in monocytes, however, was not significantly different between neonates and adults. Both hCAP18 and NGAL expression increased in an age-dependent fashion. Plasma concentration of these peptides measured by enzyme-linked immunosorbent assay was not significantly different between neonates and adults. Oral intake of 1alpha hydroxy vitamin D(3) (1alpha(OH)D(3)) in rickets patients for 4 weeks significantly increased hCAP18 expression in neutrophils compared to age-matched healthy controls without 1alpha(OH)D(3), indicating the potential of vitamin D(3) as a regulator of the innate immune response of neonates.
