“…24,25 Disturbances to integral epithelial structures create a leaky barrier that allows an increased number of inhaled irritants to infiltrate and activate immune cells in the subepithelial space. 26 Thus, the disrupted epithelial barrier evident in CRSwNP may play a key role in the pathogenesis of the disease.…”
Section: Roles Of the Upper Airway Epitheliummentioning
Background In the past, the airway epithelium was thought to be primarily an inert physical barrier. We now know that the upper airway epithelium plays a critical role in both innate and adaptive immunity, and that epithelial dysfunction is strongly associated with inflammatory airway disease. The pathogenesis of chronic rhinosinusitis is poorly understood, but growing evidence supports a key role for the airway epithelium in the pathophysiology of the disease. Objective The purpose of this study is to explore our current understanding of how dysfunction in human sinonasal epithelial cells (HSNECs) contributes to the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP) and to examine how current and developing therapies affect epithelial cell functions. Methods A literature review of papers published in English pertaining to epithelial cell dysfunction in patients with CRSwNP was performed using the PubMed database. The search utilized combinations of the following key words: sinusitis, polyps, epithelium, pathophysiology, barrier function, dendritic cells, eosinophils, T cells, complement, mucociliary clearance, vitamin D, cytokines, chemokines, taste receptors, steroids, saline, and therapy. Results HSNEC mucociliary clearance, barrier function, secretion of cytokines, influence on dendritic cells, influence on T-cells, regulation of eosinophils, vitamin D metabolism, complement production, and taste receptor function are altered in patients with CRSwNP and contribute to the pathogenesis of the disease. Current therapies utilized to manage CRSwNP counteract the effects of HSNEC dysfunction and relieve key symptoms of the disease. Conclusion HSNECs are key players in both innate and adaptive immunity, and altered epithelial functions are closely intertwined with the pathogenesis of CRSwNP. Our review supports further investigation of altered HSNEC function in patients with CRSwNP and supports development of novel epithelial-targeted therapies for its management.
“…24,25 Disturbances to integral epithelial structures create a leaky barrier that allows an increased number of inhaled irritants to infiltrate and activate immune cells in the subepithelial space. 26 Thus, the disrupted epithelial barrier evident in CRSwNP may play a key role in the pathogenesis of the disease.…”
Section: Roles Of the Upper Airway Epitheliummentioning
Background In the past, the airway epithelium was thought to be primarily an inert physical barrier. We now know that the upper airway epithelium plays a critical role in both innate and adaptive immunity, and that epithelial dysfunction is strongly associated with inflammatory airway disease. The pathogenesis of chronic rhinosinusitis is poorly understood, but growing evidence supports a key role for the airway epithelium in the pathophysiology of the disease. Objective The purpose of this study is to explore our current understanding of how dysfunction in human sinonasal epithelial cells (HSNECs) contributes to the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP) and to examine how current and developing therapies affect epithelial cell functions. Methods A literature review of papers published in English pertaining to epithelial cell dysfunction in patients with CRSwNP was performed using the PubMed database. The search utilized combinations of the following key words: sinusitis, polyps, epithelium, pathophysiology, barrier function, dendritic cells, eosinophils, T cells, complement, mucociliary clearance, vitamin D, cytokines, chemokines, taste receptors, steroids, saline, and therapy. Results HSNEC mucociliary clearance, barrier function, secretion of cytokines, influence on dendritic cells, influence on T-cells, regulation of eosinophils, vitamin D metabolism, complement production, and taste receptor function are altered in patients with CRSwNP and contribute to the pathogenesis of the disease. Current therapies utilized to manage CRSwNP counteract the effects of HSNEC dysfunction and relieve key symptoms of the disease. Conclusion HSNECs are key players in both innate and adaptive immunity, and altered epithelial functions are closely intertwined with the pathogenesis of CRSwNP. Our review supports further investigation of altered HSNEC function in patients with CRSwNP and supports development of novel epithelial-targeted therapies for its management.
“…Suzuki et al (2016) detected that nasal polyp had a higher expression of claudin (Cld)1 but lower expression of tricellulin compared with the turbinate. Integrity of the nasal epithelial TJ barrier has been shown to be compromised in Chinese patients with eosinophilic and non-eosinophilic CRSwNP transforming growth factor (TGF)-β1 seems to plays an important role in inducing TJ barrier defects (Jiao et al, 2018). Li et al showed decreased expression of epithelial zonula occludin (ZO)-1, Cld1, desmoglein (DSG)1, and DSG2 in CRSwNP and decreased expression of Cld1, DSG1, and DSG2 in CRSsNP .…”
Section: Upper Airway Epithelial Functions During Ar and Crsmentioning
Allergic rhinitis, chronic rhinosinusitis, and asthma are highly prevalent, multifactorial chronic airway diseases. Several environmental and genetic factors affect airway epithelial dynamics leading to activation of inflammatory mechanisms in the airways. This review links environmental factors to host epithelial immunity in airway diseases. Understanding altered homeostasis of the airway epithelium might provide important targets for diagnostics and therapy of chronic airway diseases.
“…TGF-β (transforming growth factor beta) is a multifunctional cytokine with important immunomodulatory and fibroblastic properties. TGF-β regulates the inflammation and remodeling of CRS [88,89], which can produce in the airway inflammatory cells and permeate in the bronchial mucosa [90]. Although nowadays five TGF-β subtypes have been identified, only three subtypes are found in the human body including TGF-β1, TGF-β2, and TGF-β3 [91].…”
Section: Regulation Of Mucins In Crsmentioning
confidence: 99%
“…This evidence suggests that TGF-β is closely related to the pathogenesis of CRSwNP. Here, the role of miR-532-3p and miR-500a-5p will be the targets to further understand the role of TGF-β in CRSwNP [ 89 , 94 , 95 ]. Fig.…”
Purpose of Review
This review highlights the expression and regulation of mucin in CRS and discusses its clinical implications.
Recent Findings
Chronic rhinosinusitis (CRS) is common chronic nasal disease; one of its main manifestations and important features is mucus overproduction. Mucin is the major component of mucus and plays a critical role in the pathophysiological changes in CRS. The phenotype of CRS affects the expression of various mucins, especially in nasal polyps (NP). Corticosteroids(CS), human neutrophil elastase (HNE), and transforming growth factor-β1 (TGF-β1) are closely related to the tissue remodeling of CRS and regulate mucin expression, mainly MUC1, MUC4, MUC5AC, and MUC5B. “It is expected that CS, HNE and TGF - β could be used to regulate the expression of mucin in CRS.” However, at present, the research on mucin is mainly focused on mucin 5AC and mucin 5B, which is bad for finding new therapeutic targets.
Summary
Investigating the expression and location of mucin in nasal mucosa and understanding the role of various inflammatory factors in mucin expression are helpful to figure out regulatory mechanisms of airway mucin hypersecretion. It is of great significance for the treatment of CRS.
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