Topical vitamin D may modulate human sinonasal mucosal responses to house dust mite antigen

Sophia W. Ma*, Jesse A. Ende, Raquel Alvarado, Jenna M. Christensen, Larry Kalish, Raymond Sacks, Raewyn Campbell, Janet Rimmer, Richard Harvey

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

Background: Respiratory epithelium is a key defense against inhaled pathogens. Vitamin D3 (VD) has been suggested to modulate airway inflammation; however, its effect on innate airway defenses, the physical barrier, mucociliary apparatus, and cytokine release remains unclear. Objective: To investigate the outcomes of VD application prior to challenge in an in vitro model of human sinonasal epithelium, through assessment of epithelial transepithelial resistance (TER), cilia beat frequency (CBF), and interleukin (IL)-6 release, and secondarily to determine whether topical VD is beneficial to patients with inflammatory sinonasal pathology. Methods: Primary human sinonasal epithelial cells from patients with eosinophilic chronic rhinosinusitis (eCRS) and healthy controls were cultured in air–liquid interface (ALI). Well-differentiated cultures from each patient were pretreated for 24 hours with 4 different VD doses. Toxicity was quantified at 24 hours in unchallenged ALI by lactate dehydrogenase (LDH) assay. Innate responses were assessed by measuring TER and CBF before and up to 24 hours after house dust mite Dermatophagoides pteronyssinus challenge. IL-6 release was evaluated 24-hour postchallenge. Results: Fifteen patients (53 ± 13.5 years, 60% females, 53% eCRS) representing 120 ALI wells were assessed. VD (0, 25, 50, 150 IU/mL) released less LDH than vehicle, indicating noncytotoxicity (0.15 ± 0.02; 0.15 ± 0.00; 0.14 ± 0.02; 0.11 ± 0.01 vs 0.17 ± 0.03, P =.004). VD increased TER for eCRS wells at 5 minutes (50 IU/mL: Δ6.76 ± 3.93 vs Δ3.87 ± 2.46, P =.04) and 24 hours (50 IU/mL: Δ0.88 ± 0.49 vs Δ0.40 ± 0.42, P =.02; 150 IU/mL: Δ1.06 ± 0.58 vs Δ0.47 ± 0.46, P =.01). CBF increased at 1 hour for eCRS wells (50 IU/mL: Δ0.62 ± 0.14 vs Δ0.41 ± 0.13, P =.001; 150 IU/ml: Δ0.60 ± 0.13 vs Δ0.38 ± 0.11, P <.001). IL-6 release was similar between normal and eCRS wells. Conclusion: Topical VD supplementation in eCRS patients may be beneficial for innate epithelial defenses. VD is noncytotoxic and does not adversely affect the physical barrier, mucociliary apparatus, or IL-6 release. Further studies should clarify its potential as a therapeutic agent.

Original languageEnglish
Pages (from-to)471-481
Number of pages11
JournalAmerican Journal of Rhinology and Allergy
Volume34
Issue number4
Early online date11 Feb 2020
DOIs
Publication statusPublished - 1 Jul 2020

Keywords

  • air–liquid interface
  • cholecalciferol
  • chronic rhinosinusitis
  • Dermatophagoides pteronyssinus
  • immunity
  • mucociliary apparatus
  • primary cell culture
  • sinonasal epithelium
  • tight junction
  • topical treatment

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