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Primary human sinonasal epithelial cell culture model for topical drug delivery in patients with chronic rhinosinusitis with nasal polyposis.
MedLine Citation:
PMID:  22309277     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Objectives  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. Key findings  Methylcholine stimulated CBF was greater in CRSwNP versus controls (ΔCBF(60min) 7.25 ± 1.02 vs 0.89 ± 1.04 Hz, respectively). Paracellular permeability was greater in CRSwNP versus controls (basolateral dextran(120min) 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.
Authors:
Benjamin S Bleier; Ryan M Mulligan; Rodney J Schlosser
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Publication Detail:
Type:  Journal Article     Date:  2011-11-13
Journal Detail:
Title:  The Journal of pharmacy and pharmacology     Volume:  64     ISSN:  2042-7158     ISO Abbreviation:  J. Pharm. Pharmacol.     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-02-07     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0376363     Medline TA:  J Pharm Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  449-56     Citation Subset:  IM    
Copyright Information:
© 2011 The Authors. JPP © 2011 Royal Pharmaceutical Society.
Affiliation:
Department of Otology and Laryngology, Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA Department of Otolaryngology-Head and Neck Surgery, Medical University of South Carolina, Charleston, SC, USA.
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