Interleukin 13 exposure enhances vitamin D-mediated expression of the human cathelicidin antimicrobial peptide 18/LL-37 in bronchial epithelial cells.
Schrumpf. J A JA; van Sterkenburg. M A J A MA; Verhoosel. R M RM; Zuyderduyn. S S; Hiemstra. P S PS
Key Findings
- IL‑13 increases the expression of the enzyme CYP27B1 that converts inactive vitamin D (25D) into its active form (1,25D) in bronchial epithelial cells.
- With IL‑13 present, vitamin D (25D) more strongly raises levels of the antimicrobial peptide LL‑37 and the vitamin D‑inactivating enzyme CYP24A1.
- Vitamin D receptor (VDR) levels were not significantly changed by IL‑13, indicating the effect is mainly through increased activation of vitamin D rather than receptor abundance.
Practical Outcomes
- For biohackers, the main takeaway is that vitamin D supplementation could be more effective at boosting lung antimicrobial defenses when Th2 inflammation (e.g., allergic asthma) is active. However, because IL‑13 itself isn’t easily manipulated, the study doesn’t provide a direct new protocol—just reinforces the idea that maintaining adequate vitamin D status may support innate immunity, especially in people with allergic airway conditions.
Summary
The study shows that the asthma‑related cytokine IL‑13 makes airway cells better at turning vitamin D into its active form, which then boosts production of the antimicrobial peptide LL‑37. In simple terms, when IL‑13 is present, taking vitamin D may lead to higher levels of LL‑37, a molecule that helps fight infections in the lungs.
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.
Study Information
pubmed
2012
2012-10-08T00:00:00.000Z
10.1128/iai.06224-11