IL-13 exposure enhances vitamin D-mediated expression of the human cathelicidin antimicrobial peptide-hCAP18/LL-37 in bronchial epithelial cells.
Infect Immun. 2012 Oct 8;
Authors: Schrumpf JA, van Sterkenburg MA, Verhoosel RM, Zuyderduyn S, Hiemstra PS
Abstract
Vitamin D is an important regulator of the expression of antimicrobial peptides, and vitamin D deficiency is associated with respiratory infections. Regulating expression of antimicrobial peptides such as the human cathelicidin antimicrobial peptide (hCAP)18/LL-37 by vitamin D in bronchial epithelial cells requires local conversion of 25(OH)vitaminD(3) (25D(3)) into its bioactive metabolite 1,25(OH)(2)vitaminD(3) (1,25D(3)) by CYP27B1. Low circulating vitamin D-levels in childhood asthma are associated with more severe exacerbations, which are often associated with infections. Atopic asthma is accompanied by Th2 driven inflammation mediated by cytokines such as IL-4 and IL-13, and the effect of these cytokines on vitamin D metabolism and hCAP-18/LL-37 expression is unknown. Therefore we investigated this in well-differentiated bronchial epithelial cells. To this end, cells were treated with IL-13 with and without 25D(3) and expression of hCAP18/LL-37, CYP27B1, the 1,25D(3) inactivating enzyme CYP24A1, and vitamin D receptor was assessed by quantitative PCR. We show that IL-13 enhances the ability of 25D(3) to increase expression of hCAP18/LL-37 and CYP24A1. In addition, exposure to IL-13 resulted in increased CYP27B1 expression, whereas VDR expression was not significantly affected. The enhancing effect of IL-13 on 25D(3)-mediated expression of hCAP18/LL-37 was further confirmed using SDS-PAGE Western Blot and immunofluorescence staining. In conclusion, we demonstrate that IL-13 induces vitamin D(-)dependent hCAP18/LL-37 expression, most likely by increasing CYP27B1. These data suggest that Th2 cytokines regulate the vitamin D metabolic pathway in bronchial epithelial cells.
PMID: 23045480 [PubMed – as supplied by publisher]
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