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.

PPARγ agonists upregulate the barrier function of tight junctions via a PKC pathway in human nasal epithelial cells

2010 ◽  
Vol 61 (6) ◽  
pp. 489-498 ◽  
Author(s):  
Noriko Ogasawara ◽  
Takashi Kojima ◽  
Mitsuru Go ◽  
Tsuyoshi Ohkuni ◽  
Jun-ichi Koizumi ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Tight Junctions ◽  
Barrier Function ◽  
Nasal Epithelial Cells ◽  
Human Nasal Epithelial Cells ◽  
Pparγ Agonists

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.

Urban Particulate Matters May Affect Endoplasmic Reticulum Stress and Tight Junction Disruption in Nasal Epithelial Cells

2021 ◽  
pp. 194589242110040
Author(s):  
Soo Kyoung Park ◽  
Sun Hee Yeon ◽  
Mi-Ra Choi ◽  
Seung Hyeon Choi ◽  
Sung Bok Lee ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Epithelial Cells ◽  
Er Stress ◽  
Stress Responses ◽  
Barrier Function ◽  
Epithelial Barrier ◽  
In Vivo Models ◽  
Nasal Epithelial Cells ◽  
Human Nasal Epithelial Cells ◽  
Mucosal Barrier Function

Background Exposure to airborne urban particulate matter (UPM) has been closely related to the development and aggravation of respiratory disease, including sinonasal disorders. Objective The aims of this study were to investigate the effect of UPM on nasal epithelial tight junctions (TJs) and mucosal barrier function and delineate the underlying mechanism by using both in vitro and in vivo models. Methods In this study, human nasal epithelial cells (hNECs) and BALB/c mice were exposed to UPMs. UPM 1648a and 1649 b were employed. TJ and endoplasmic reticulum (ER) stress marker expression was measured using western blot analysis and immunofluorescence. TJ integrity and nasal epithelial barrier function were evaluated by transepithelial electric resistance (TER) and paracellular flux. In addition, the effects of N‐acetyl‐L‐cysteine (NAC) on UPM-induced nasal epithelial cells were investigated. Results UPM significantly impaired the nasal epithelial barrier, as demonstrated by decreased protein expression of TJ and ER stress markers in human nasal epithelial cells. This finding was in parallel to reduced transepithelial electrical resistance and increased fluorescein isothiocyanate–dextran permeability. Pretreatment with NAC decreased the degree of UPM-mediated ER stress and restored nasal epithelial barrier disruption in human nasal epithelial cells (hNEC) and the nasal mucosa of experimental animals. Conclusion These data suggest that UPMs may induce nasal epithelial barrier dysfunction by targeting TJs and ER stress could be related in this process. Based on these results, we suggest that suppression of this process with an inhibitor targeting ER stress responses could represent a novel promising therapeutic target in UPM-induced sinonasal disease.

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.

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.

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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