Remodelling of nasal mucosa in mild and severe persistent allergic rhinitis with special reference to the distribution of collagen, proteoglycans, and lymphatic vessels

Kim, T. H.; Lee, J. Y.; Lee, H. M.; Cho, W. S.; Ju, Young‐Kyu; Park, E. H.; Kim, K. W.

doi:10.1111/j.1365-2222.2010.03612.x

Cited by 37 publications

(45 citation statements)

References 50 publications

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“…Extending our attention to human asthmatics, there is a report that lymphatics were decreased in the airway walls in cases of fatal asthma 39 . Conversely, in patients with allergic rhinitis, the densities of LVs were increased in allergic nasal mucosa compared with those in healthy nasal mucosa 40 . Notably, neither articles investigated the mechanisms underlying the observed phenomena.…”

Section: Articlementioning

confidence: 75%

TH2 cells and their cytokines regulate formation and function of lymphatic vessels

et al. 2015

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Lymphatic vessels (LVs) are critical for immune surveillance and involved in the pathogenesis of diverse diseases. LV density is increased during inflammation; however, little is known about how the resolution of LVs is controlled in different inflammatory conditions. Here we show the negative effects of T helper type 2 (T H 2) cells and their cytokines on LV formation. IL-4 and IL-13 downregulate essential transcription factors of lymphatic endothelial cells (LECs) and inhibit tube formation. Co-culture of LECs with T H 2 cells also inhibits tube formation, but this effect is fully reversed by interleukin (IL)-4 and/or IL-13 neutralization. Furthermore, the in vivo blockade of IL-4 and/or IL-13 in an asthma model not only increases the density but also enhances the function of lung LVs. These results demonstrate an antilymphangiogenic function of T H 2 cells and their cytokines, suggesting a potential usefulness of IL-4 and/or IL-13 antagonist as therapeutic agents for allergic asthma through expanding LV mediated-enhanced antigen clearance from the inflammatory sites.

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Section: Articlementioning

confidence: 75%

TH2 cells and their cytokines regulate formation and function of lymphatic vessels

et al. 2015

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“…Remodeling is not only linked to chronic inflammatory lower airway disorders, like cystic fibrosis and asthma [3], but also takes place in the upper airways during chronic inflammation like allergic rhinitis or CRS. It can cause pathological changes in the lamina propria, airway epithelium, and submucosal regions in CRS, including inflammatory cell infiltrates, basement membrane thickening, subepithelial edema, and fibrosis [4]. Accordingly, CRSwNP is characterized by diffuse sinus mucosal thickening and benign edematous polyp outgrowths with a histological pattern of chronic mononuclear cell and eosinophil infiltration and airway remodeling, including epithelial goblet cell hyperplasia, an increase in α-smooth muscle actin (α-SMA) and myofibroblasts, and an increase in basement membrane and submucosal collagen deposition [5-10].…”

Section: Introductionmentioning

confidence: 99%

TGF-β1 Induces Epithelial-Mesenchymal Transition of Chronic Sinusitis with Nasal Polyps through MicroRNA-21

Zhu

et al. 2019

Int Arch Allergy Immunol

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Objectives: To characterize the epithelial-mesenchymal transition (EMT) in chronic rhinosinusitis with nasal polyps (CRSwNP) and to investigate the mechanism by which microRNA-21 (miR-21) regulates EMT in CRSwNP. Method: (1) Tissue experiments: Mucosa tissues were collected from 13 patients with CRSwNP and 12 patients with CRS without nasal polyps (CRSsNP), as well as 11 patients without CRS (controls). Protein localization and quantification were achieved by immunofluorescence staining and Western blotting, involving the epithelial marker protein E-cadherin and the mesenchymal marker proteins α-smooth muscle actin (α-SMA), fibronectin, and vimentin. Quantitative RT-PCR was used to detect the relative expression levels of miR-21 and TGF-β1 mRNAs. (2) Cellular experiments: Primary human nasal epithelial cells (PHNECs) treated with TGF-β1, or TGF-β1 with miR-21 inhibitor, or miR-21 mimics alone were observed for morphology changes under a phase-contrast microscope. The expression levels of epithelial/mesenchymal marker proteins were determined as aforementioned. PTEN and phosphorylated Akt were detected by Western blotting. Results: (1) Tissue experiments: Compared with the CRSsNP and control groups, the expression of E-cadherin was downregulated in the CRSwNP group, whereas the expression of TGF-β1, α-SMA, fibronectin, and vimentin was upregulated. The expression levels of miR-21 and TGF-β1 mRNAs in CRSwNP were significantly higher than those in CRSsNP and controls. (2) Cellular experiments: TGF-β1 induced EMT-like transformation in PHNECs, featured by changes in cell morphology and upregulation of mesenchymal proteins and miR-21. The miR-21 inhibitor, as well as the Akt-specific inhibitor, suppressed TGF-β1-induced EMT. Mechanically, downregulation of miR-21 resulted in increased PTEN and decreased Akt phosphorylation. Furthermore, overexpression of miR-21 had the opposite effects. Conclusions: Our findings suggest that the TGF-β1-miR-21-PTEN-Akt axis may contribute to the pathogenesis of CRSwNP. miR-21 might be a reliable target for treating nasal polyp genesis through EMT suppression. Moreover, miR-21 inhibitors could be a novel class of antipolyp drug that modulates PTEN expression and Akt activation. In addition, further investigation regarding the reason underlying miR-21 overexpression in CRSwNP could provide a molecular target for novel treatment strategies for nasal polyposis.

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“…Allergic rhinitis and chronic rhinosinusitis with polyposis are examples of persistent inflammatory diseases of the upper airway dominated by CD4 + Th2 effector cells secreting IL-4, IL-5, and IL-13 in response to commonly inhaled antigens [2]–[4]. Recently, it has been recognized that Th2-dominated upper airway inflammation may lead to long-term airway remodeling [5]. In the Th1/Th2 paradigm, the Th1 cytokine IFN-γ is considered counter-regulatory to Th2 responses [6].…”

Section: Introductionmentioning

confidence: 99%

“…MMPs are a subfamily of zinc- and calcium-dependent enzymes and are responsible for many physiological and pathological processes [22]. Previous studies have shown increased expression of MMPs in the patients with asthma and allergic rhinitis [5], [23]. MMP-9 is highly increased in bronchial biopsies from asthmatics compared with normal subjects [24].…”

Section: Introductionmentioning

confidence: 99%

Regulation of Nasal Airway Homeostasis and Inflammation in Mice by SHP-1 and Th2/Th1 Signaling Pathways

Cho

Lane

et al. 2014

PLoS ONE

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Allergic rhinitis is a chronic inflammatory disease orchestrated by Th2 lymphocytes. Src homology 2 domain-containing protein tyrosine phosphatase (SHP)-1 is known to be a negative regulator in the IL-4α/STAT-6 signaling pathway of the lung. However, the role of SHP-1 enzyme and its functional relationship with Th2 and Th1 cytokines are not known in the nasal airway. In this study, we aimed to study the nasal inflammation as a result of SHP-1 deficiency in viable motheaten (mev) mice and to investigate the molecular mechanisms involved. Cytology, histology, and expression of cytokines and chemokines were analyzed to define the nature of the nasal inflammation. Targeted gene depletion of Th1 (IFN-γ) and Th2 (IL-4 and IL-13) cytokines was used to identify the critical pathways involved. Matrix metalloproteinases (MMPs) were studied to demonstrate the clearance mechanism of recruited inflammatory cells into the nasal airway. We showed here that mev mice had a spontaneous allergic rhinitis-like inflammation with eosinophilia, mucus metaplasia, up-regulation of Th2 cytokines (IL-4 and IL-13), chemokines (eotaxin), and MMPs. All of these inflammatory mediators were clearly counter-regulated by Th2 and Th1 cytokines. Deletion of IFN-γ gene induced a strong Th2-skewed inflammation with transepithelial migration of the inflammatory cells. These findings suggest that SHP-1 enzyme and Th2/Th1 paradigm may play a critical role in the maintenance of nasal immune homeostasis and in the regulation of allergic rhinitis.

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Remodelling of nasal mucosa in mild and severe persistent allergic rhinitis with special reference to the distribution of collagen, proteoglycans, and lymphatic vessels

Abstract: These results suggest that the altered distribution pattern of collagen, proteoglycans, and lymphatic vessels could potentially modulate the remodelling of nasal mucosa in mild and severe persistent allergic nasal mucosa.

Cited by 37 publications

References 50 publications

TH2 cells and their cytokines regulate formation and function of lymphatic vessels

TH2 cells and their cytokines regulate formation and function of lymphatic vessels

TGF-β1 Induces Epithelial-Mesenchymal Transition of Chronic Sinusitis with Nasal Polyps through MicroRNA-21

Regulation of Nasal Airway Homeostasis and Inflammation in Mice by SHP-1 and Th2/Th1 Signaling Pathways

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