Abstract
The human paranasal sinuses are the major source of intrinsic nitric oxide (NO) production in the human airway. NO plays several roles in the maintenance of physiological homeostasis and the regulation of airway inflammation through the expression of three NO synthase (NOS) isoforms. Measuring NO levels can contribute to the diagnosis and assessment of allergic rhinitis (AR) and chronic rhinosinusitis (CRS). In symptomatic AR patients, pro-inflammatory cytokines upregulate the expression of inducible NOS (iNOS) in the inferior turbinate. Excessive amounts of NO cause oxidative damage to cellular components, leading to the deposition of cytotoxic substances. CRS phenotype and endotype classifications have provided insights into modern treatment strategies. Analyses of the production of sinus NO and its metabolites revealed pathobiological diversity that can be exploited for useful biomarkers. Measuring nasal NO based on different NOS activities is a potent tool for specific interventions targeting molecular pathways underlying CRS endotype-specific inflammation. We provide a comprehensive review of the functional diversity of NOS isoforms in the human sinonasal system in relation to these two major nasal disorders’ pathologies. The regulatory mechanisms of NOS expression associated with the substrate bioavailability indicate the involvement of both type 1 and type 2 immune responses.
Highlights
Nitric oxide (NO), a paramagnetic molecule with an odd number of electrons, is a radical with extreme reactivity that is responsible for many of its biological effects
These findings suggest that sinus ciliated cells may serve vital physiological functions in nonspecific host defense mechanisms against bacterial or viral infections, and they may help preserve the sterile microenvironment via mucociliary clearance systems
These results indicate that the maxillary and anterior ethmoid sinuses are the dominant sources of nasal nitric oxide (NO) detected in the middle meatus (MM) area, and they emphasize the role of the paranasal sinuses as a physiological NO reservoir
Summary
Nitric oxide (NO), a paramagnetic molecule with an odd number of electrons, is a radical with extreme reactivity that is responsible for many of its biological effects. Epithelial motile cilia covering a large area of the human paranasal sinuses produce bactericidal levels of NO that increase ciliary beating, which is the airway’s major physical defense. A nonspecific NOS inhibitor, i.e., NG-nitro-L-arginine methyl ester (L-NAME), inhibited the L-arginine-induced increase in CBF [29] The immunoreactivity of both iNOS and eNOS was observed in the ciliated epithelial cells, with eNOS staining being more intense [29]. Products with a bitter taste that are secreted from common microorganisms are detected by the receptors of upper-airway epithelial cells These products elicit T2R (taste family 2 bitter receptor proteins)-activated downstream responses to enhance the production of NO with bactericidal activities [33,34,35]. Lipopolysaccharide (LPS)-stimulated exosomes in mucus sampled from the human nose induced a fourfold increase in NO production by promoting cellular iNOS signaling pathways in in vitro cultures [43]
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