TY - JOUR
T1 - Responses of well-differentiated human sinonasal epithelial cells to allergen exposure and environmental pollution in chronic rhinosinusitis
AU - Ahmadzada, Sejad
AU - Ende, Jesse A.
AU - Alvarado, Raquel
AU - Christensen, Jenna M.
AU - Kim, Joo-Hye
AU - Rimmer, Janet
AU - Harvey, Richard J.
PY - 2019/11/1
Y1 - 2019/11/1
N2 - 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.
AB - 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.
KW - air–liquid interface
KW - chronic rhinosinusitis
KW - chronic rhinosinusitis with nasal polyps
KW - chronic rhinosinusitis without nasal polyps
KW - diesel particular matter
KW - house dust mite
KW - respiratory epithelium
KW - tissue culture
UR - http://www.scopus.com/inward/record.url?scp=85068384310&partnerID=8YFLogxK
U2 - 10.1177/1945892419853103
DO - 10.1177/1945892419853103
M3 - Article
C2 - 31256605
AN - SCOPUS:85068384310
SN - 1945-8924
VL - 33
SP - 624
EP - 633
JO - American Journal of Rhinology and Allergy
JF - American Journal of Rhinology and Allergy
IS - 6
ER -