Article ; Online: Interleukin 13 exposure enhances vitamin D-mediated expression of the human cathelicidin antimicrobial peptide 18/LL-37 in bronchial epithelial cells.
2012 Volume 80, Issue 12, Page(s) 4485–4494
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 ( ...
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. |
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MeSH term(s) | Adjuvants, Immunologic/genetics ; Adjuvants, Immunologic/metabolism ; Antimicrobial Cationic Peptides ; Bronchi/cytology ; Bronchi/drug effects ; Bronchi/metabolism ; Cathelicidins/genetics ; Cathelicidins/metabolism ; Cells, Cultured ; Cholecalciferol/genetics ; Cholecalciferol/metabolism ; Cholecalciferol/pharmacology ; Epithelial Cells/drug effects ; Epithelial Cells/metabolism ; Humans ; Interleukin-13/genetics ; Interleukin-13/metabolism ; Interleukin-13/pharmacology ; Receptors, Calcitriol/genetics ; Receptors, Calcitriol/metabolism ; Up-Regulation/drug effects ; Vitamin D/analogs & derivatives ; Vitamin D/genetics ; Vitamin D/metabolism |
Chemical Substances | Adjuvants, Immunologic ; Antimicrobial Cationic Peptides ; Cathelicidins ; Interleukin-13 ; Receptors, Calcitriol ; Vitamin D (1406-16-2) ; Cholecalciferol (1C6V77QF41) ; ropocamptide (3DD771JO2H) |
Language | English |
Publishing date | 2012-10-08 |
Publishing country | United States |
Document type | Journal Article ; Research Support, Non-U.S. Gov't |
ZDB-ID | 218698-6 |
ISSN | 1098-5522 ; 0019-9567 |
ISSN (online) | 1098-5522 |
ISSN | 0019-9567 |
DOI | 10.1128/IAI.06224-11 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
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