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

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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.

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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.

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

Clinical & Experimental Allergy ◽

10.1111/cea.12644 ◽

2016 ◽

Vol 46 (3) ◽

pp. 449-460 ◽

Cited By ~ 20

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

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

10.26226/morressier.5acdc65ed462b8029238de3b ◽

2018 ◽

Author(s):

qian xiu

Keyword(s):

Epithelial Cells ◽

Nasal Polyps ◽

Caspase 3 ◽

Nasal Epithelial Cells

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Increased Expression of TXNIP Facilitates Oxidative Stress in Nasal Epithelial Cells of Patients With Chronic Rhinosinusitis With Nasal Polyps

American Journal of Rhinology and Allergy ◽

10.1177/1945892420982411 ◽

2020 ◽

pp. 194589242098241

Author(s):

Hai Lin ◽

Guangyi Ba ◽

Ru Tang ◽

Mingxian Li ◽

Zhipeng Li ◽

...

Keyword(s):

Oxidative Stress ◽

Epithelial Cells ◽

Real Time ◽

Chronic Rhinosinusitis ◽

Western Blotting ◽

Real Time Pcr ◽

Nasal Polyps ◽

Sod Activity ◽

Nasal Tissue ◽

Sod Assay

Background Oxidative stress plays crucial roles in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP). Thioredoxin-interacting protein (TXNIP) is essential in the process of triggering oxidative stress. However, its role and mechanism in CRSwNP remain unclear. The present study sought to explore the role and mechanism of TXNIP in the pathogenesis of CRSwNP. Methods Western blotting, real-time PCR and immunohistochemistry (IHC) were employed to assess TXNIP, thioredoxin (TRX) expression in nasal tissue samples from patients with CRSwNP and control subjects. MDA level and SOD activity in nasal tissue homogenates were measured using MDA and SOD Assay Kit. To evaluate the role and mechanism of TXNIP in CRSwNP, human nasal epithelial cells (HNECs) were cultured and stimulated using TXNIP siRNA, with or without N-acetylcysteine (NAC, an ROS scavenger). Western blotting, real-time PCR, ROS detecting dye DCFH-DA, MDA and SOD Assay Kit were performed to assess the effects and mechanisms of stimulators on the cells. Results We found significantly increased levels of TXNIP and decreased levels of TRX protein, mRNA, positive cells, increased MDA level and decreased SOD activity in CRSwNP patients compared with control subjects. In vitro study, significantly altered levels of TXNIP, TRX, MDA, SOD and ROS in HNECs were found following treatment of TXNIP siRNA with or without NAC on HNECs. Conclusion TXNIP expression was increased and TRX expression was decreased in CRSwNP at both protein and mRNA levels. MDA levels were increased and SOD activities were decreased in CRSwNP. TXNIP may have negative association with TRX, and then decrease SOD activities and increase MDA levels, resulting in the upregulation of ROS and oxidative stress in HNECs, which may play a pivotal role in the pathogenesis of CRSwNP. Future studies are expected to further explore the role and mechanism of TXNIP in CRSwNP.

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

10.21203/rs.3.rs-118180/v1 ◽

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.

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