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Interleukin 13 exposure enhances vitamin D-mediated expression of the human cathelicidin antimicrobial peptide 18/LL-37 in bronchial epithelial cells.

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 18 (hCAP18)/LL-37, by vitamin D in bronchial epithelial cells requires local conversion of 25(OH)-vitamin D(3) (25D(3)) into its bioactive metabolite, 1,25(OH)(2)-vitamin D(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 interleukin 4 (IL-4) and IL-13, and the effect of these cytokines on vitamin D metabolism and hCAP18/LL-37 expression is unknown. Therefore, we investigated this with 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 vitamin D receptor (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 blotting 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.

journal_name

Infect Immun

journal_title

Infection and immunity

authors

Schrumpf JA,van Sterkenburg MA,Verhoosel RM,Zuyderduyn S,Hiemstra PS

doi

10.1128/IAI.06224-11

subject

Has Abstract

pub_date

2012-12-01 00:00:00

pages

4485-94

issue

eissn

0019-9567

issn

1098-5522

pii

IAI.06224-11

journal_volume

pub_type

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Interleukin 13 exposure enhances vitamin D-mediated expression of the human cathelicidin antimicrobial peptide 18/LL-37 in bronchial epithelial cells.