Primary human sinonasal epithelial cell culture model for topical drug delivery in patients with chronic rhinosinusitis with nasal polyposis.
OBJECTIVE
The primary human sinonasal epithelial cell culture (HSNEC) allows for in-vitro modelling of mucosal responses to topical therapy. Cultures grown from healthy donors may underestimate changes in individuals with chronic sinonasal disease thereby yielding inaccurate results with respect to this large patient population. The purpose of this study was to analyse HSNECs derived from patients with chronic rhinosinusitis with nasal polyposis (CRSwNP) to determine whether expected disease dependent variables salient to topical drug delivery persist in culture.


METHODS
Cultures were grown from patients with CRSwNP. Ciliary beat frequency (CBF) (basal and stimulated), permeability (trans and paracellular), inflammatory response, and glucocorticoid dose response were measured and compared with healthy controls.


RESULTS
Methylcholine stimulated CBF was greater in CRSwNP versus controls (ΔCBF(60 min) 7.25 ± 1.02 vs 0.89 ± 1.04 Hz, respectively). Paracellular permeability was greater in CRSwNP versus controls (basolateral dextran(120 min) 18.97 ± 3.90 vs 11.31 ± 4.35 µg/ml, respectively). Lipopolysaccharide (0.1 mg/ml) stimulated interleukin-6 (IL-6) and IL-8 secretion was increased in CRSwNP versus controls (IL-6 Δbaseline 1738.72 ± 654.82 vs 1461.61 ± 533.51%, respectively; IL-8 Δbaseline 137.11 ± 0.83 vs 111.27 ± 0.67%, respectively). CRSwNP cultures were more sensitive than controls to dexamethasone (1 µg/ml) dependent IL-6 and IL-8 suppression.


CONCLUSIONS
HSNECs derived from patients with CRSwNP retained their primary phenotype with respect to ciliary function, epithelial permeability, irritant induced inflammatory cytokine secretion, and glucocorticoid dose response.
Department of Otology and Laryngology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA, USA. bleierb@gmail.com
Benjamin S
BS
Bleier
Ryan M
RM
Mulligan
Rodney J
RJ
Schlosser
D000287:Administration, Topical; D016022:Case-Control Studies; D002478:Cells, Cultured / Q000187:drug effects; D002908:Chronic Disease; D002923:Cilia / Q000187:drug effects; D003907:Dexamethasone / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects; D005938:Glucocorticoids / Q000627:therapeutic use*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008954:Models, Biological; D009297:Nasal Mucosa / Q000187:drug effects*; D009298:Nasal Polyps / Q000188:drug therapy* / Q000235:genetics; D010641:Phenotype; D012220:Rhinitis / Q000188:drug therapy*; D012852:Sinusitis / Q000188:drug therapy* / Q000235:genetics
D005938:Glucocorticoids; D015850:Interleukin-6; D016209:Interleukin-8; D003907:Dexamethasone