The Expression of 11β-Hydroxysteroid Dehydrogenase Type 1 and 2 in Nasal Polyp–Derived Epithelial Cells and its Possible Contribution to Glucocorticoid Activation in Nasal Polyp

Kook, Jin Ho; Kim, Hyun Jin; Kim, Kyung Won; Park, Se Jin; Kim, Tae Hoon; Lim, Sae Hee; Kang, Sung Hoon; Lee, Sang Hag

doi:10.2500/ajra.2015.29.4185

Cited by 4 publications

(2 citation statements)

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“…In this line, intrapolyp steroid injections appear to be effective and safe for the treatment of nasal polyps (Kırıs et al, 2016). Additionally, it has been shown that polypderived epithelial cells produce cortisol, which may be involved in the anti-inflammatory response established when patients receive treatment with glucocorticoid for nasal polyps (Kook et al, 2015). The elevation of this metabolite in the non-allergic CRSwNP patients might point to a specific pathway to cope with inflammation.…”

Section: Discussionmentioning

confidence: 99%

Understanding Systemic and Local Inflammation Induced by Nasal Polyposis: Role of the Allergic Phenotype

Delgado-Dolset

Obeso

Sánchez-Solares

et al. 2021

Front. Mol. Biosci.

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Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized by persistent symptoms associated to the development of nasal polyps. To this day, the molecular mechanisms involved are still not well defined. However, it has been suggested that a sustained inflammation as allergy is involved in its onset. In this exploratory study, the aim was to investigate the effect of the allergic status in the development of CRSwNP. To achieve this, we recruited 22 patients with CRSwNP and classified them in non-allergic and allergic using ImmunoCAP ISAC molecular diagnosis. Plasma samples were analyzed using liquid chromatography coupled to mass spectrometry (LC-MS). Subsequently, significant metabolites from plasma that were commercially available were then analyzed by targeted analysis in some nasal polyps. Additionally, nasal polyp and nasal mucosa samples were examined for eosinophils, neutrophils, CD3+ and CD11c+ cells, as well as collagen deposition and goblet cell hyperplasia. We found that 9 out of the 22 patients were sensitized to some aeroallergens (named as allergic CRSwNP). The other 13 patients had no sensitizations (non-allergic CRSwNP). Regarding metabolomics, bilirubin, cortisol, lysophosphatidylcholines (LPCs) 16:0, 18:0 and 20:4 and lysophosphatidylinositol (LPI) 20:4, which are usually related to a sustained allergic inflammation, were unexpectedly increased in plasma of non-allergic CRSwNP compared to allergic CRSwNP. LPC 16:0, LPC 18:0 and LPI 20:4 followed the same trend in nasal polyp as they did in plasma. Comparison of nasal polyps with nasal mucosa showed a significant increase in eosinophils (p < 0.001) and neutrophils (p < 0.01) in allergic CRSwNP. There were more eosinophils in polyps of non-allergic CRSwNP than in their nasal mucosa (p < 0.01). Polyps from non-allergic CRSwNP had less eosinophils than the polyps of allergic CRSwNP (p < 0.05) and reduced amounts of collagen compared to their nasal mucosa (p < 0.001). Our data suggests that there is a systemic inflammatory response associated to CRSwNP in the absence of allergy, which could be accountable for the nasal polyp development. Allergic CRSwNP presented a higher number of eosinophils in nasal polyps, suggesting that eosinophilia might be connected to the development of nasal polyps in this phenotype.

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Section: Discussionmentioning

confidence: 99%

Understanding Systemic and Local Inflammation Induced by Nasal Polyposis: Role of the Allergic Phenotype

Delgado-Dolset

Obeso

Sánchez-Solares

et al. 2021

Front. Mol. Biosci.

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“…Studies like this should ultimately lead to new and more effective therapies for CRS, but the mainstay for medical management continues to be glucocorticosteroids. In this issue, Kook et al 2 assess polyp-derived epithelial cell expression of enzymes involved in glucocorticosteroid metabolism and correlate enzyme expression with cortisol levels. Their results suggest that expression of the enzyme 11β-hydroxysteroid dehydrogenase may mediate the anti-inflammatory effect of glucocorticosteroids by increasing levels of endogenous cortisol.…”

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confidence: 99%

Advancing the Understanding of Complex Rhinologic Problems

Turner¹

2015

Am J Rhinol�Allergy

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Advancing the understanding of complex rhinologic problems E ach issue of the American Journal of Rhinology and Allergy presents cutting edge basic and clinical research within the fields of allergy and rhinologic diseases. The current issue is no exception, with a diverse array of innovative studies from a worldwide collection of contributors. Readers will find basic and translational studies that explore the immunologic basis of allergic rhinitis (AR) and chronic rhinosinusitis (CRS), as well as clinical and technical studies that explore issues ranging from rhinoscleroma to cerebrospinal fluid leak repair. The July/ August issue certainly highlights the mission of the AJRA, with subject matter for basic scientists and clinicians alike. Chronic rhinosinusitis and allergic rhinitis are becoming increasingly prevalent, however, our understanding of the pathophysiology and immunologic contributors to disease development and progression remain poorly understood. Leading off the current issue, Shimizu et al 1 investigate the impact of tissue remodeling and the extrinsic coagulation cascade on the pathogenesis of CRS. They found that the coagulation pathway proteins, tissue factor and tissue factor pathway inhibitor, are expressed in nasal secretions and nasal epithelial cells and hypothesize that upregulation of these factors may play an important role in fibrin deposition, tissue remodeling, and nasal polyp architecture. Studies like this should ultimately lead to new and more effective therapies for CRS, but the mainstay for medical management continues to be glucocorticosteroids. In this issue, Kook et al 2 assess polyp-derived epithelial cell expression of enzymes involved in glucocorticosteroid metabolism and correlate enzyme expression with cortisol levels. Their results suggest that expression of the enzyme 11␤-hydroxysteroid dehydrogenase may mediate the anti-inflammatory effect of glucocorticosteroids by increasing levels of endogenous cortisol. CRS results in many symptoms that adversely affect quality of life, with olfactory dysfunction representing one of the primary complaints of many patients. As detailed by Joo et al 3 in this issue, loss of the sense of smell can be associated with both depressed mood and suicidal ideation. Unfortunately, regardless of etiology, there are few proven interventions for the long-term management of olfactory dysfunction. Improvement in olfactory outcomes following endoscopic sinus surgery is reported by Gupta et al, 4 however, aggressive removal of polyps from the olfactory cleft itself remains somewhat controversial. Kuperan et al 5 evaluated the benefit of endoscopic olfactory cleft polyp surgery on olfaction in a randomized singleblind study. Their results showed a statistically significant improvement in objective olfactory outcomes six months postoperatively for patients receiving surgery of the olfactory cleft. Though long-term data is still lacking, the current report suggests that directly addressing olfactory cleft polyps during endoscopic sinus surgery may prov...

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Role of NLRP3 Inflammasome in Eosinophilic and Non-eosinophilic Chronic Rhinosinusitis with Nasal Polyps

Lin

et al. 2016

Inflammation

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The pathophysiologic mechanisms of human chronic rhinosinusitis with nasal polyps (CRSwNP) remain unclear. We aimed to elucidate expression and biologic role of NLRP3 inflammasome in CRSwNP. Immunohistochemistry (IHC) was conducted to assess NLRP3 immunolabeling, real-time polymerase chain reaction (PCR) was used for IL-9 and NLRP3, and caspase-1 level quantitation in CRSwNP and control subjects. In addition, enzyme-linked immunosorbent assay (ELISA) was employed for analyzing concentrations of IL-1β and IL-18 in the homogenates prepared from tissue specimens. Moreover, human nasal epithelial cells (HNECs) were used to evaluate the effects of lipopolysaccharide (LPS) and glyburide on NLRP3 inflammasome signaling pathway. Results showed that NLRP3 and caspase-1 were overexpressed in CRSwNP, especially in eosinophilic CRSwNP (ECRSwNP). Interestingly, NLRP3 expression had close correlation to that of caspase-1. Concentrations of IL-1β and IL-18 were elevated. NLRP3 inflammasome signaling pathway was augmented by LPS but suppressed by glyburide. In conclusion, NLRP3 inflammasome signaling pathway played a pro-inflammatory role in the pathogenesis of CRSwNP, especially in ECRSwNP. NLRP3 inflammasome signaling pathway was augmented by LPS, but suppressed by glyburide.

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The Expression of 11β-Hydroxysteroid Dehydrogenase Type 1 and 2 in Nasal Polyp–Derived Epithelial Cells and its Possible Contribution to Glucocorticoid Activation in Nasal Polyp

Abstract: Analysis of these results indicated that 11β-HSD1 expressed in polyp-derived epithelial cells may be involved in the anti-inflammatory function of glucocorticoid in the treatment of nasal polyps, which contributes to increased levels of endogenous cortisol.

Cited by 4 publications

References 36 publications

Understanding Systemic and Local Inflammation Induced by Nasal Polyposis: Role of the Allergic Phenotype

Understanding Systemic and Local Inflammation Induced by Nasal Polyposis: Role of the Allergic Phenotype

Advancing the Understanding of Complex Rhinologic Problems

Role of NLRP3 Inflammasome in Eosinophilic and Non-eosinophilic Chronic Rhinosinusitis with Nasal Polyps

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