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

ORL ◽  
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

<b><i>Objective:</i></b> Na<sup>+</sup>-K<sup>+</sup>-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. <b><i>Methods:</i></b> 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. <b><i>Results:</i></b> 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. <b><i>Conclusion:</i></b> 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.

scholarly journals Involvement of the Extracellular Matrix Proteins Periostin and Tenascin C in Nasal Polyp Remodeling by Regulating the Expression of MMPs

2020 ◽  
Author(s):  
Kun Du ◽  
Min Wang ◽  
Nan Zhang ◽  
Ping Wang ◽  
Pei Yu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Epithelial Cells ◽  
Chronic Rhinosinusitis ◽  
Nasal Polyp ◽  
Nasal Polyps ◽  
Ex Vivo ◽  
Tissue Remodeling ◽  
Tenascin C ◽  
Protein Levels ◽  
Control Subjects

Abstract Background: Tissue remodeling caused by increased MMPs is involved in the pathogenesis of chronic rhinosinusitis with nasal polyposis (CRSwNP). We previously found higher levels of periostin and tenascin C in CRSwNPs, but whether they are associated with the dysregulation of MMPs is unknown. Therefore, the present study aimed to investigate the regulatory roles of two ECM proteins in the expression of MMPs in nasal polyps.Methods：The concentrations of MMP-2, MMP-3, MMP-7, MMP-8, MMP-9, MMP-12, MMP-13, TIMP-1, TIMP-2, TIMP-3, TIMP-4, periostin, and tenascin C in tissue homogenates of 51 patients with chronic rhinosinusitis with and without nasal polyps and 15 control subjects were measured and their correlations were analyzed. Primary human nasal polyp fibroblasts and epithelial cells were stimulated ex vivo with periostin and tenascin C and the gene expression of MMPs and TIMPs was determined by means of real-time PCR.Results: The protein levels of MMP-3, MMP-7, MMP-8, MMP-9, TIMP-1, TIMP-2, periostin, and tenascin C were significantly higher in patients with CRSwNPs than in healthy control subjects. Periostin was positively correlated with MMP-3 and TIMP-2, and tenascin C was positively correlated with MMP-3, MMP-7, MMP-8, MMP-9 and TIMP-2. Periostin stimulated the gene expression of MMP-3, MMP-7, and MMP-9 in fibroblasts and MMP-7 in epithelial cells ex vivo. Tenascin C stimulated the expression of MMP-3, MMP-8, and MMP-9 in epithelial cells, but not in fibroblasts. The expression of TIMPs in fibroblasts and epithelial cells was affected by neither periostin nor tenascin C. Conclusions：Periostin and tenascin C might be involved in the remodeling of nasal polyps by regulating the expression of different MMPs in epithelial cells and fibroblasts. Our findings have the potential to identify key factors of tissue remodeling in CRSwNPs.

Macrolide Treatment Decreased the Size of Nasal Polyps and IL-8 Levels in Nasal Lavage

2000 ◽  
Vol 14 (3) ◽  
pp. 143-148 ◽  
Author(s):  
Takechiyo Yamada ◽  
Shigeharu Fujieda ◽  
Shigehito Mori ◽  
Hideyuki Yamamoto ◽  
Hitoshi Saito
Keyword(s):  
Cystic Fibrosis ◽  
Epithelial Cells ◽  
Chronic Rhinosinusitis ◽  
Nasal Polyps ◽  
Experimental Studies ◽  
Nasal Lavage ◽  
Nasal Epithelial Cells ◽  
Diffuse Panbronchiolitis ◽  
Human Nasal Epithelial Cells

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.

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

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.

Role of IFN-γ, IL-13, and IL-17 on mucociliary differentiation of nasal epithelial cells in chronic rhinosinusitis with nasal polyps

2016 ◽  
Vol 46 (3) ◽  
pp. 449-460 ◽  
Author(s):  
J. Jiao ◽  
S. Duan ◽  
N. Meng ◽  
Y. Li ◽  
E. Fan ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Chronic Rhinosinusitis ◽  
Nasal Polyps ◽  
Nasal Epithelial Cells ◽  
Ifn Γ ◽  
Mucociliary Differentiation

scholarly journals Association between methylation in nasal epithelial TSLP gene and chronic rhinosinusitis with nasal polyps

2019 ◽  
Vol 15 (1) ◽  
Author(s):  
Jingyun Li ◽  
Jian Jiao ◽  
Yunbo Gao ◽  
Yuan Zhang ◽  
Luo Zhang
Keyword(s):  
Dna Methylation ◽  
Chronic Rhinosinusitis ◽  
Nasal Polyps ◽  
Inferior Turbinate ◽  
Nasal Resistance ◽  
Total Ige ◽  
Control Subjects ◽  
Human Nasal Epithelial Cells ◽  
Serum Total Ige ◽  
And Control

Abstract Background This study was performed to determine whether there was any association between abnormal DNA methylation of a thymic stromal lymphopoietin (TSLP) locus and pathogenesis of chronic rhinosinusitis (CRS). Methods A total of 48 CRS patients with nasal polyps (CRSwNP), 28 CRS patients without nasal polyps (CRSsNP) and 21 control subjects were enrolled into the study; and evaluated for serum total IgE level, olfactory score and nasal resistance. Samples were obtained from nasal polyps of CRSwNP patients, ethmoid mucosae of CRSsNP patients and inferior turbinate (IT) mucosa of control subjects during surgery, and used to isolate purified primary human nasal epithelial cells (HNECs). Genomic DNA was extracted from purified primary HNECs of each subject and DNA methylation ratios for a selected region of the TSLP gene were screened the using MassARRAY EpiTYPER. Results A total of 17 CpG units were analyzed; of which two CpG units (CpG3 and 22:23:24) had increased methylation ratios in the CRSwNP patients compared to the CRSsNP and control subjects after correction for false discovery rate (FDR) (Q < 0.1). The methylation ratios at both CpG3 and CpG22:23:24 units were positively correlated with olfactory score (r = 0.41, P = 0.0001; r = 0.25, P = 0.021) and unilateral nasal resistance at 75 Pa (r = 0.24, P = 0.04; r = 0.24, P = 0.036) and 150 Pa (r = 0.34, P = 0.004; r = 0.25, P = 0.031). Total nasal resistance at 75 Pa/150 Pa or serum total IgE levels were not correlated with the methylation ratios at either CpG unit. Conclusions Increased DNA methylation at the TSLP locus is likely to be associated with CRSwNP pathogenesis; however these findings need to be confirmed in larger multicentre group studies.

scholarly journals Hypomethylation of the IL8 promoter in nasal epithelial cells of patients with chronic rhinosinusitis with nasal polyps

2019 ◽  
Vol 144 (4) ◽  
pp. 993-1003.e12 ◽  
Author(s):  
Jingyun Li ◽  
Jian Jiao ◽  
Ming Wang ◽  
Yunbo Gao ◽  
Ying Li ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Chronic Rhinosinusitis ◽  
Nasal Polyps ◽  
Nasal Epithelial Cells

scholarly journals Effects of HMGB1 on Tricellular Tight Junctions via TGF-β Signaling in Human Nasal Epithelial Cells

2021 ◽  
Vol 22 (16) ◽  
pp. 8390
Author(s):  
Kizuku Ohwada ◽  
Takumi Konno ◽  
Takayuki Kohno ◽  
Masaya Nakano ◽  
Tsuyoshi Ohkuni ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Tight Junctions ◽  
Chronic Rhinosinusitis ◽  
Kinase Inhibitor ◽  
High Mobility ◽  
Epithelial Barrier ◽  
Type I ◽  
Nasal Epithelial Cells ◽  
Human Nasal Epithelial Cells ◽  
Matrigel Culture

The airway epithelium of the human nasal mucosa acts as a physical barrier that protects against inhaled substances and pathogens via bicellular and tricellular tight junctions (bTJs and tTJs) including claudins, angulin-1/LSR and tricellulin. High mobility group box-1 (HMGB1) increased by TGF-β1 is involved in the induction of nasal inflammation and injury in patients with allergic rhinitis, chronic rhinosinusitis, and eosinophilic chronic rhinosinusitis. However, the detailed mechanisms by which this occurs remain unknown. In the present study, to investigate how HMGB1 affects the barrier of normal human nasal epithelial cells, 2D and 2.5D Matrigel culture of primary cultured human nasal epithelial cells were pretreated with TGF-β type I receptor kinase inhibitor EW-7197 before treatment with HMGB1. Knockdown of angulin-1/LSR downregulated the epithelial barrier. Treatment with EW-7197 decreased angulin-1/LSR and concentrated the expression at tTJs from bTJs and increased the epithelial barrier. Treatment with a binder to angulin-1/LSR angubindin-1 decreased angulin-1/LSR and the epithelial barrier. Treatment with HMGB1 decreased angulin-1/LSR and the epithelial barrier. In 2.5D Matrigel culture, treatment with HMGB1 induced permeability of FITC-dextran (FD-4) into the lumen. Pretreatment with EW-7197 prevented the effects of HMGB1. HMGB1 disrupted the angulin-1/LSR-dependent epithelial permeability barriers of HNECs via TGF-β signaling in HNECs.

scholarly journals Expression of ICAM-1 by IFN-γ and IL-4 in Cultured Normal Human Nasal Epithelial Cells

2000 ◽  
Vol 11 (2) ◽  
pp. 261-266
Author(s):  
Yong-Dae Kim ◽  
Jun Chul Park ◽  
Joon Hyuk Lee ◽  
Jung Suck Cho ◽  
Jae Uk Lee ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Nasal Epithelial Cells ◽  
Human Nasal Epithelial Cells ◽  
Normal Human ◽  
Ifn Γ

scholarly journals WS06.2 Altered epithelial Cl − secretion in primary human nasal epithelial cells of patients with chronic rhinosinusitis

2016 ◽  
Vol 15 ◽  
pp. S9-S10
Author(s):  
J.J. Salomon ◽  
T. Albrecht ◽  
H. Scheuermann ◽  
I. Baumann ◽  
M.A. Mall
Keyword(s):  
Epithelial Cells ◽  
Chronic Rhinosinusitis ◽  
Nasal Epithelial Cells ◽  
Cl Secretion ◽  
Human Nasal Epithelial Cells

Expression of TLR2 and TLR4 Messenger RNA in the Epithelial Cells of the Nasal Airway

2005 ◽  
Vol 19 (3) ◽  
pp. 236-239 ◽  
Author(s):  
Zhen Dong ◽  
Zhanquan Yang ◽  
Chengshuo Wang
Keyword(s):  
Epithelial Cells ◽  
Chronic Rhinosinusitis ◽  
Nasal Mucosa ◽  
Messenger Rna ◽  
Nasal Epithelial Cells ◽  
Tlr4 Mrna ◽  
Human Nasal Epithelial Cells ◽  
Local Host ◽  
Adult Volunteers

Background Epithelium of nasal mucosa is the first line of defense against invading pathogens. This study investigated the expression of Toll-like receptor (TLR) 2 and TLR4 in epithelial cells of nasal mucosa and understood the role of TLRs in the innate immunity of nasal mucosa. Methods Human nasal epithelial cells were obtained by scraping the middle one-third of inferior turbinates from 30 patients with chronic rhinosinusitis and 20 healthy adult volunteers. The epithelial cells are made into smears. In situ hybridization was performed for TLR2 and TLR4 messenger RNA (mRNA). Results TLR2 and TLR4 mRNA were expressed in the nasal epithelial cells. The expression of the two genes was significantly higher in the chronic rhinosinusitis group than in the normal control (TLR2, t = 8.605, p < 0.0005; TLR4, t = 9.050, p < 0.0005). Conclusion This study is the first to establish the presence of both TLR2 and TLR4 mRNA on epithelial cells of nasal mucosa, and their expression can be up-regulated in infectious conditions. These results show that TLR2 and TLR4 may play a important role in local host defense of nasal mucosa.

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