Responses of well-differentiated human sinonasal epithelial cells to allergen exposure and environmental pollution in chronic rhinosinusitis

Sejad Ahmadzada*, Jesse A. Ende, Raquel Alvarado, Jenna M. Christensen, Joo-Hye Kim, Janet Rimmer, Richard J. Harvey

*Corresponding author for this work

Research output: Contribution to journalArticle

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Abstract

Background: Evidence suggests that intrinsic cell dysfunction leads to dysregulated immune responses to environmental triggers in chronic rhinosinusitis (CRS). Although epidemiological and in vivo studies support this theory, in vitro studies are lacking. Methods: Epithelial cells from human sinonasal mucosa were cultured using an air–liquid interface culture model producing a well-differentiated phenotype. Specimens were characterized as chronic rhinosinusitis with (CRSwNP) or without (CRSsNP) nasal polyps and healthy control mucosa. Culture wells were exposed to house dust mite (HDM), diesel exhaust particles (DPM), or a combination (HDM + DPM) over 24 hours and responses in the 3 groups compared. Ciliary beat frequency (CBF) and transepithelial electrical resistance (TEER) were measured to assess mucociliary and barrier function, respectively. Interleukin-6 (IL-6) and 33 (IL-33) were measured after 24 hours. Results following challenge testing are expressed as fold change from baseline. Results: Baseline CBF was lower in CRSsNP compared with control (5.27 ± 0.51 Hz vs 5.88 ± 1.22 Hz, P =.003). HDM significantly reduced CBF and TEER in the CRSwNP group compared with its vehicle (CBF: 0.55 ± 0.25 vs 1.03 ± 0.22, P <.001; TEER: 0.54 [0.13] Ω cm2 vs 0.93 [0.5] Ω cm2, P =.001). In CRSwNP and CRSsNP, HDM induced an increase in IL-6 compared with its vehicle (CRSwNP: 81.11 [67.19] pg/mL vs 3.15 [44.64] pg/mL, P =.016; CRSsNP: 321.46 [182.04] pg/mL vs 21.54 [53.93] pg/mL, P =.004). Results are expressed as median (interquartile range) and in IL-33 in CRswNP (84.04 [69.96] pg/mL vs 16.62 [20.19] pg/mL, P =.025). Exposure to DPM did not affect CBF, TEER, and cytokine release in all groups. Conclusion: CRSwNP and CRSsNP cells exhibit altered responses particularly to HDM even after they have been removed from their host and cultured in vitro, suggesting an intrinsic cell dysfunction of the upper airway epithelium.

Original languageEnglish
Pages (from-to)624-633
Number of pages10
JournalAmerican Journal of Rhinology and Allergy
Volume33
Issue number6
Early online date29 Jun 2019
DOIs
Publication statusPublished - 1 Nov 2019

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Keywords

  • air–liquid interface
  • chronic rhinosinusitis
  • chronic rhinosinusitis with nasal polyps
  • chronic rhinosinusitis without nasal polyps
  • diesel particular matter
  • house dust mite
  • respiratory epithelium
  • tissue culture

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