Dying fibroblasts stimulates proliferation of living nasal epithelial cells via caspase-3 activation in nasal polyps

Recently, epidemiologic and experimental studies have been reported that long-term macrolides are effective for the treatment of chronic airway inflammatory diseases including diffuse panbronchiolitis, chronic rhinosinusitis, and cystic fibrosis (Jaffe A, Francis J, Rosenthal M, et al. Long-term azithromycin may improve lung function in children with cystic fibrosis. Lancet 351:420, 1998), and that macrolides can directly reduce the production of IL-8 by nasal epithelial cells (Suzuki H, Shimomura A, Ikeda K, et al. Inhibitory effect of macrolides on interleukin-8 secretion from cultured human nasal epithelial cells. Laryngoscope 107:1661–1666, 1997). In this study we administered macrolides with 14-membered rings to patients with nasal polyps due to chronic rhinosinusitis for at least 3 months and measured the IL-8 level in nasal lavage from those patients. The IL-8 levels in nasal lavage from patients with nasal polyps were reduced during macrolide treatment. There was significant correlation between decreased IL-8 levels in nasal lavage and the clinical effect of macrolides on the size of the nasal polyps. In the group whose polyps were reduced in size, the IL-8 levels dramatically decreased from 231.2 pg/mL to 44.0 pg/mL (p < 0.05), and were significantly higher before macrolide treatment than those in the group whose polyps showed no change (p < 0.005). This reduction in IL-8 may be an important aspect of the effect of macrolide treatment on nasal polyps in chronic rhinosinusitis.

Download Full-text

S100A8 Enhances IL-1β Production from Nasal Epithelial Cells in Eosinophilic Chronic Rhinosinusitis

10.21203/rs.3.rs-934588/v1 ◽

2021 ◽

Author(s):

Ayaka Nakatani ◽

Takeshi Tsuda ◽

Yohei Maeda ◽

Masaki Hayama ◽

Daisuke Okuzaki ◽

...

Keyword(s):

Epithelial Cells ◽

Chronic Rhinosinusitis ◽

Nasal Polyps ◽

Expression Profiles ◽

Allergic Inflammation ◽

Gene Expression Profiles ◽

Interleukin 1Β ◽

Nasal Epithelial Cells ◽

Human Nasal Epithelial Cells ◽

Eosinophilic Chronic Rhinosinusitis

Abstract Chronic rhinosinusitis is classified into eosinophilic chronic rhinosinusitis (ECRS) and non-eosinophilic chronic rhinosinusitis (NECRS). ECRS is a refractory allergic disease involving a variety of immune and epithelial cells. S100A8 is a damage-associated molecular pattern that is closely related to allergic inflammation. However, the pathological implications of S100A8 in ECRS have not been clarified. We evaluated the role of S100A8 in the pathogenesis of ECRS. Gene expression profiles of nasal polyps obtained from patients with ECRS or NECRS were evaluated using RNA sequencing. S100A8 was identified as a significantly upregulated gene in nasal polyps associated with ECRS. Immunohistochemistry consistently revealed intense S100A8 staining in nasal polyps from patients with ECRS. Human nasal epithelial cells expressed the receptor for advanced glycation end products and Toll-like receptor 4. Recombinant S100A8 protein induced interleukin-1β secretion in human nasal epithelial cells. Our data demonstrate that S100A8 results in production of interleukin-1β in the nasal epithelium, which may be involved in the pathogenesis of ECRS.

Download Full-text

The Expression and Regulation of Na+-K+-ATPase in Nasal Epithelial Cells of Chronic Rhinosinusitis with Nasal Polyps

ORL ◽

10.1159/000517101 ◽

2021 ◽

pp. 1-8

Author(s):

Guangyi Ba ◽

Ru Tang ◽

Song Mao ◽

Zhipeng Li ◽

Haibo Ye ◽

...

Keyword(s):

Epithelial Cells ◽

Chronic Rhinosinusitis ◽

Nasal Polyps ◽

Cell Permeability ◽

Mrna Levels ◽

Nasal Epithelial Cells ◽

Protein Levels ◽

Control Subjects ◽

Human Nasal Epithelial Cells ◽

Ifn Γ

Objective: Na+-K+-ATPase (NKA) is essential in maintaining cell permeability, reserving potential energy, and preventing cellular edema. Nevertheless, how NKA expression is altered and regulated in chronic rhinosinusitis with nasal polyps (CRSwNPs) remain uncertain. Therefore, the present study aimed to explore the expression and regulation of NKA in CRSwNP. Methods: NKA immunolabeling was assessed by the immunohistochemistry method, NKA protein levels were detected with the Western blotting method, and mRNA levels of NKA and aquaporin-5 (AQP5) were assayed by real-time PCR in nasal tissues from CRSwNP and control subjects. The co-localization of NKA with inflammatory cells was evaluated by immunofluorescence staining. In addition, human nasal epithelial cells (HNECs) were cultured and stimulated using various stimulators to evaluate the regulation of NKA. Results: We found significantly decreased NKA positive cells, NKA protein levels, and mRNA levels of NKA and AQP5 in nasal tissues from CRSwNP patients compared to control subjects, especially in eosinophilic CRSwNP. Furthermore, NKA mRNA levels in HNECs were downregulated by staphylococcal enterotoxin B (SEB), lipopolysaccharides (LPSs), inflammatory cytokine (IFN)-γ, IL-4, IL-13, and IL-1β. Conclusion: NKA and AQP5 expressions were decreased in CRSwNP. NKA in HNECs could be suppressed by SEB, LPS, IFN-γ, IL-4, IL-13, and IL-1β. Impairment of NKA may contribute to the genesis and development of CRSwNP via inducing AQP5 downregulation and edema.

Download Full-text

Cytokine-Induced Modulation of SARS-CoV2 Receptor Expression in Primary Human Nasal Epithelial Cells

Pathogens ◽

10.3390/pathogens10070848 ◽

2021 ◽

Vol 10 (7) ◽

pp. 848

Author(s):

Mahnaz Ramezanpour ◽

Harrison Bolt ◽

Karen Hon ◽

George Spyro Bouras ◽

Alkis James Psaltis ◽

...

Keyword(s):

Epithelial Cells ◽

Viral Entry ◽

Nasal Polyps ◽

Receptor Expression ◽

Host Cells ◽

Upper Respiratory Tract ◽

Nasal Epithelial Cells ◽

Human Nasal Epithelial Cells ◽

Inflammatory State ◽

Sinonasal Mucosa

Background: Viral entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) via the spike protein enables endocytosis into host cells using the ACE2 receptor and TMPRSS2. The frequent upper respiratory tract symptoms of COVID-19 and the localization of the virus to the nasopharynx, the most common site of swabbing, indicate that the sinonasal mucosa may play an important role in SARS-CoV2 infection and viral replication. Methods: This paper investigates the presence of ACE2 receptor and TMPRESS2 expression in the primary human nasal epithelial cells (HNECs) from the following: chronic rhinosinusitis without nasal polyps (CRSsNP), CRS with nasal polyps (CRSwNP) and control (non-CRS) patients, and maps the expression changes when exposed to Th1, Th2, Th17-associated cytokines. Results: We found that ACE2 and TMPRSS2 expression was higher in control HNECs than CRSwNP HNECs, and that both ACE2 and TMPRSS2 were downregulated further by Th2 cytokines in CRSwNP HNECs. Conclusions: This indicates an immune dysregulated state of CRSwNP mucosa, which normally contributes to a chronic inflammatory state, and might support an altered susceptibility to SARS-CoV2 infection and transmission.

Download Full-text

5-Oxo-ETE from Nasal Epithelial Cells Upregulates Eosinophil Cation Protein by Eosinophils in Nasal Polyps in vitro

International Archives of Allergy and Immunology ◽

10.1159/000489819 ◽

2018 ◽

Vol 177 (2) ◽

pp. 107-115 ◽

Cited By ~ 4

Author(s):

Lin Lin ◽

Zheng Chen ◽

Xinyue Tang ◽

Fei Dai ◽

Jinjin Wei ◽

...

Keyword(s):

Epithelial Cells ◽

Nasal Polyps ◽

Nasal Epithelial Cells

Download Full-text

HSP70 Expression in Nasal Epithelial Cells in Patients with Chronic Rhinosinusitis with Nasal Polyps

Problems of Cryobiology and Cryomedicine ◽

10.15407/cryo29.02.166 ◽

2019 ◽

Vol 29 (2) ◽

pp. 166-166

Author(s):

Anatolii Onishchenko ◽

◽

Anton Tkachenko ◽

Elina Kharchenko ◽

Diana Sklyaruk ◽

...

Keyword(s):

Epithelial Cells ◽

Chronic Rhinosinusitis ◽

Nasal Polyps ◽

Hsp70 Expression ◽

Nasal Epithelial Cells

Download Full-text

TGF-β1 downregulates CFTR expression and function in nasal polyps of non-CF patients

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00048.2004 ◽

2005 ◽

Vol 288 (1) ◽

pp. L77-L83 ◽

Cited By ~ 29

Author(s):

Virginie Prulière-Escabasse ◽

Pascale Fanen ◽

Anne Catherine Dazy ◽

Emmanuèle Lechapt-Zalcman ◽

Dominique Rideau ◽

...

Keyword(s):

Epithelial Cells ◽

Protein Expression ◽

Nasal Polyps ◽

Nasal Polyposis ◽

Cftr Gene ◽

Nasal Epithelial Cells ◽

Human Nasal Epithelial Cells ◽

And Function ◽

Tgf Β1

Nasal polyposis is a chronic inflammatory disease of the upper airways. It has been suggested that ion transports and CFTR expression could be modified in epithelial cells from nasal polyps of non-cystic fibrosis patients. We compared human nasal epithelial cells from nasal polyps (NP) with control nasal mucosa (CM). The level of CFTR mRNA was studied by Northern blot analysis and protein expression was studied by immunoprecipitation both ex vivo and in vitro in primary cultures of human nasal epithelial cells at the air-liquid interface. Ion transports were evaluated by short-circuit measurements in vitro. CFTR gene and protein expressions were significantly decreased in NP native tissues and in culture on day 4, when a global defect of ion transports was observed in NP cultures, but not in CM. We evaluated the effect of transforming growth factor (TGF)-β1 on CFTR expression and function in NP cultures on day 14 and showed, for the first time, that TGF-β1 was able to significantly downregulate the level of CFTR mRNA and cAMP-dependent current in NP cultures. Finally, we showed that the effects of TGF-β1 on ion transports could be reversed after 48-h removal of TGF-β1 in NP cultures. In conclusion, our data strongly suggest that chronic inflammation in nasal polyposis downregulates CFTR gene and protein expression.

Download Full-text