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.

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

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.

Thymic stromal lymphopoietin enhances tight-junction barrier function of human nasal epithelial cells

2009 ◽  
Vol 338 (2) ◽  
pp. 283-293 ◽  
Author(s):  
Ryuta Kamekura ◽  
Takashi Kojima ◽  
Jun-ichi Koizumi ◽  
Noriko Ogasawara ◽  
Makoto Kurose ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Tight Junction ◽  
Barrier Function ◽  
Thymic Stromal Lymphopoietin ◽  
Nasal Epithelial Cells ◽  
Human Nasal Epithelial Cells

scholarly journals Elovanoids Counteract Inflammatory Signaling, Autophagy, Endoplasmic Reticulum Stress, and Senescence Gene Programming in Human Nasal Epithelial Cells Exposed to Allergens

Pharmaceutics ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 113
Author(s):  
Alfredo Resano ◽  
Surjyadipta Bhattacharjee ◽  
Miguel Barajas ◽  
Khanh V. Do ◽  
Roberto Aguado-Jiménez ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Epithelial Cells ◽  
Inflammatory Responses ◽  
House Dust Mites ◽  
Poly I:C ◽  
Lipid Mediator ◽  
Omega 3 ◽  
Nasal Epithelial Cells ◽  
Human Nasal Epithelial Cells

To contribute to further understanding the cellular and molecular complexities of inflammatory-immune responses in allergic disorders, we have tested the pro-homeostatic elovanoids (ELV) in human nasal epithelial cells (HNEpC) in culture challenged by several allergens. ELV are novel bioactive lipid mediators synthesized from the omega-3 very-long-chain polyunsaturated fatty acids (VLC-PUFA,n-3). We ask if: (a) several critical signaling events that sustain the integrity of the human nasal epithelium and other organ barriers are perturbed by house dust mites (HDM) and other allergens, and (b) if ELV would participate in beneficially modulating these events. HDM is a prevalent indoor allergen that frequently causes allergic respiratory diseases, including allergic rhinitis and allergic asthma, in HDM-sensitized individuals. Our study used HNEpC as an in vitro model to study the effects of ELV in counteracting HDM sensitization resulting in inflammation, endoplasmic reticulum (ER) stress, autophagy, and senescence. HNEpC were challenged with the following allergy inducers: LPS, poly(I:C), or Dermatophagoides farinae plus Dermatophagoides pteronyssinus extract (HDM) (30 µg/mL), with either phosphate-buffered saline (PBS) (vehicle) or ELVN-34 (500 nM). Results show that ELVN-34 promotes cell viability and reduces cytotoxicity upon HDM sensitization of HNEpC. This lipid mediator remarkably reduces the abundance of pro-inflammatory cytokines and chemokines IL-1β, IL-8, VEGF, IL-6, CXCL1, CCL2, and cell adhesion molecule ICAM1 and restores the levels of the pleiotropic anti-inflammatory IL-10. ELVN-34 also lessens the expression of senescence gene programming as well as of gene transcription engaged in pro-inflammatory responses. Our data also uncovered that HDM triggered the expression of key genes that drive autophagy, unfolded protein response (UPR), and matrix metalloproteinases (MMP). ELVN-34 has been shown to counteract these effects effectively. Together, our data reveal a novel, pro-homeostatic, cell-protective lipid-signaling mechanism in HNEpC as potential therapeutic targets for allergies.

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