<i>In vitro</i>Effects of Anthocyanidins on Sinonasal Epithelial Nitric Oxide Production and Bacterial Physiology

Hariri, Benjamin M.; Payne, Sakeena J.; Chen, Bei; Mansfield, Corrine; Doghramji, Laurel; Adappa, Nithin D.; Palmer, James N.; Kennedy, David W.; Niv, Masha Y.; Lee, Robert J.

doi:10.2500/ajra.2016.30.4331

Cited by 25 publications

(26 citation statements)

References 83 publications

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“…6-Methoxy-N-(3-sulfopropyl)quinolinium (SPQ) was loaded for 6 h incubation with apical PBS containing 20 mM SPQ at 37°C and imaged with a DAPI filter set (49000; Chroma Technology). Fluorescence was normalized to time 0 (F/F 0 ), as previously described (30,44) (45) or ciliaFA (46) as previously described (30,38,47)…”

Section: Par-2 Rt-pcr Western Blotting and Immunofluorescencementioning

confidence: 99%

Protease‐activated receptor 2 activates airway apical membrane chloride permeability and increases ciliary beating

et al. 2017

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Mucociliary clearance, driven by the engine of ciliary beating, is the primary physical airway defense against inhaled pathogens and irritants. A better understanding of the regulation of ciliary beating and mucociliary transport is necessary for identifying new receptor targets to stimulate improved clearance in airway diseases, such as cystic fibrosis and chronic rhinosinusitis. In this study, we examined the protease-activated receptor (PAR)-2, a GPCR previously shown to regulate airway cell cytokine and mucus secretion, and transepithelial Cl current. PAR-2 is activated by proteases secreted by airway neutrophils and pathogens. We cultured various airway cell lines, primary human and mouse sinonasal cells, and human bronchial cells at air-liquid interface and examined them using molecular biology, biochemistry, and live-cell imaging. We found that PAR-2 is expressed basolaterally, where it stimulates both intracellular Ca release and Ca influx, which activates low-level nitric oxide production, increases apical membrane Cl permeability ∼3-5-fold, and increases ciliary beating ∼20-50%. No molecular or functional evidence of PAR-4 was observed. These data suggest a novel and previously overlooked role of PAR-2 in airway physiology, adding to our understanding of the role of this receptor in airway Ca signaling and innate immunity.-McMahon, D. B., Workman, A. D., Kohanski, M. A., Carey, R. M., Freund, J. R., Hariri, B. M., Chen, B., Doghramji, L. J., Adappa, N. D., Palmer, J. N., Kennedy, D. W., Lee, R. J. Protease-activated receptor 2 activates airway apical membrane chloride permeability and increases ciliary beating.

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Section: Par-2 Rt-pcr Western Blotting and Immunofluorescencementioning

confidence: 99%

Protease‐activated receptor 2 activates airway apical membrane chloride permeability and increases ciliary beating

et al. 2017

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“…In addition to published studies pointing to dysmorphology and dysfunction of mucociliary clearance mechanisms associated with tobacco smoke exposure, there is a growing awareness of the role of the regulation of ciliary function modulation by nitric oxide (NO) (Jain et al, 1993; Jiao et al, 2011; Maniscalco et al, 2016; Ostrowski et al, 2012; Sisson et al, 2009; Vleeming et al, 2002; Wyatt, 2015; Zhou et al, 2009, 2011). While a variety of agents such as alcohol, tobacco smoke and microbiological products have been shown to affect this mechanism, there is little data to inform how NO modulation of ciliary function might be associated with e-cigarette use (Hariri et al, 2016; Sisson et al, 2009; Zhou et al, 2009). Given the evidence from previous studies (Cao et al, 2013; Cueto & Pryor, 1994; Ferrer-Sueta & Radi, 2009) that NO may contribute to an inflammatory milieu and the generation of toxic metabolites, it is plausible that recurrent exposures over time may be contributory to pathologies such as chronic obstructive respiratory disease (COPD) and chronic rhinosinusitis.…”

Section: Introductionmentioning

confidence: 99%

Temporal structure/function variation in cultured differentiated human nasal epithelium associated with acute single exposure to tobacco smoke or E-cigarette vapor

Carson

Zhou

Brighton

et al. 2017

Inhalation Toxicology

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Objective Mucociliary clearance sustains a baseline functionality and an “on demand” capability to upregulate clearance upon irritant exposure involving mucus hypersecretion and accelerated ciliary beat frequency (CBF) modulated by nitric oxide (NO). This study characterized these elements as well as cellular and exogenous NO concentrations subsequent to a single exposure to tobacco smoke (TS) or e-cigarette vapor (EV) on cultured human airway epithelium. Materials and methods Air-liquid interface (ALI) airway epithelial cultures per nonsmoking human subjects were subjected to single TS or EV exposures. Measures of ciliary function and secretion were performed and cellular and exogenous NO concentrations under control and experimental conditions were assessed. Results Both TS and EV exposures resulted similar patterns of decline in CBF within 1 min of the completion of exposure followed by a gradual return often exceeding baseline within 1 h. Post-exposure examination of exposed cultures suggested morphologic differences in secretory function relative to controls. The relative NO concentrations of TS and EV chamber air were sharply different with EV NO being only slightly elevated relative to cellular NO production. Discussion and conclusions Epithelial remodeling and mucociliary dysfunction have been clearly associated with TS exposure. However, information contrasting epithelial structure/function following a single acute TS or EV exposure is limited. This study demonstrates a similar pattern of epithelial response to acute TS or EV exposure. Inasmuch as NO may contribute to an inflammatory milieu and generation of toxic metabolites, it is plausible that recurrent exposures over time may be contributory to chronic pathologies.

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“…NO also diffuses into the mucous and directly targets bacteria and viruses. 2,3 The clinical importance of T2R38 as a biomarker for CRS has been further elucidated by studying polymorphisms in T2R38 that produce decreased receptor functionality and lead to an increased susceptibility to gram-negative infection and recalcitrant CRS. 4,5 Furthermore, the genotype of T2R38 can predict surgical outcomes of patients with nonpolyposis CRS and even biofilm formation.…”

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confidence: 99%

Nitric Oxide Production is Stimulated by Bitter Taste Receptors Ubiquitously Expressed in the Sinonasal Cavity

Yan

Hahn

McMahon

et al. 2017

Am J Rhinol�Allergy

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In vitroEffects of Anthocyanidins on Sinonasal Epithelial Nitric Oxide Production and Bacterial Physiology

Abstract: ABSTRACT

Cited by 25 publications

References 83 publications

Protease‐activated receptor 2 activates airway apical membrane chloride permeability and increases ciliary beating

Protease‐activated receptor 2 activates airway apical membrane chloride permeability and increases ciliary beating

Temporal structure/function variation in cultured differentiated human nasal epithelium associated with acute single exposure to tobacco smoke or E-cigarette vapor

Nitric Oxide Production is Stimulated by Bitter Taste Receptors Ubiquitously Expressed in the Sinonasal Cavity

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