Divergent effects of Nitric oxide on airway epithelial cell activation

Neri, Tommaso; Conti, Ilaria; Cerri, Chiara; Tavanti, Laura; Paggiaro, Pierluigi; Celi, Alessandro

doi:10.4067/s0716-97602010000400012

Cited by 1 publication

(2 citation statements)

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“…In summary, we show that the GSNO formulation containing ascorbic acid in addition to dispersing biofilms potentiates the efficacy of gentamicin to effectively reduce the viable bacterial density in the biofilm established on the surface of mucociliary-differentiated sinonasal epithelial cells without inducing a pro-inflammatory response or cell death. CRS patients usually have chronic sinonasal inflammation, which may be reduced by GSNO given the anti-inflammatory effects of NO under physiological conditions. , Further, GSNO treatment may improve the mucociliary clearance function of the sinonasal epithelium, thus preventing the acute exacerbations and disease perpetuation in these patients. Since GSNO is already present in our bodies and we consume ascorbic acid daily at much higher concentrations, we envision that this formulation may be developed into therapy to treat flare-ups, prevent biofilm formation, and enhance mucociliary clearance in CRS patients.…”

Section: Discussionmentioning

confidence: 99%

“…CRS patients usually have chronic sinonasal inflammation, which may be reduced by GSNO given the anti-inflammatory effects of NO under physiological conditions. 85 , 86 Further, GSNO treatment may improve the mucociliary clearance function of the sinonasal epithelium, thus preventing the acute exacerbations and disease perpetuation in these patients. Since GSNO is already present in our bodies and we consume ascorbic acid daily at much higher concentrations, we envision that this formulation may be developed into therapy to treat flare-ups, prevent biofilm formation, and enhance mucociliary clearance in CRS patients.…”

Section: Discussionmentioning

confidence: 99%

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S-Nitrosoglutathione Reduces the Density of Staphylococcus aureus Biofilms Established on Human Airway Epithelial Cells

et al. 2022

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Patients with chronic rhinosinusitis (CRS) often show persistent colonization by bacteria in the form of biofilms which are resistant to antibiotic treatment. One of the most commonly isolated bacteria in CRS is Staphylococcus aureus (S. aureus). Nitric oxide (NO) is a potent antimicrobial agent and disperses biofilms efficiently. We hypothesized that S-nitrosoglutathione (GSNO), an endogenous NO carrier/donor, synergizes with gentamicin to disperse and reduce the bacterial biofilm density. We prepared GSNO formulations which are stable up to 12 months at room temperature and show the maximum amount of NO release within 1 h. We examined the effects of this GSNO formulation on the S. aureus biofilm established on the apical surface of the mucociliary-differentiated airway epithelial cell cultures regenerated from airway basal (stem) cells from cystic fibrosis (CF) and CRS patients. We demonstrate that for CF cells, which are defective in producing NO, treatment with GSNO at 100 μM increased the NO levels on the apical surface and reduced the biofilm bacterial density by 2 log units without stimulating pro-inflammatory effects or inducing epithelial cell death. In combination with gentamicin, GSNO further enhanced the killing of biofilm bacteria. Compared to placebo, GSNO significantly increased the ciliary beat frequency (CBF) in both infected and uninfected CF cell cultures. The combination of GSNO and gentamicin also reduced the bacterial density of biofilms grown on sinonasal epithelial cells from CRS patients and improved the CBF. These findings demonstrate that GSNO in combination with gentamicin may effectively reduce the density of biofilm bacteria in CRS patients. GSNO treatment may also enhance the mucociliary clearance by improving the CBF.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%