Protease-dependent activation of nasal polyp epithelial cells by airborne fungi leads to migration of eosinophils and neutrophils

Shin, Seung‐Heon; Lee, Young-Ho; Jeon, Chang‐Ho

doi:10.1080/00016480500395179

Cited by 67 publications

(57 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Our findings are in keeping with previous studies that have reported the increase of pro-inflammatory cytokines, such as IL-8 [39], [59], [60] and chemokines, as GM-CSF [39], [61], [62], eotaxin [63], and MCP-1 [64] in CRSwNP, compared to control nasal mucosa. These cytokines and chemokines have been implicated in eosinophil inflammation in nasal polyps [1], [39], [62], [63] and are downregulated with glucocorticoid [39], [62], [65], [66] or anti-leukotriene [67] treatments.…”

Section: Discussionsupporting

confidence: 93%

Reconstituted Human Upper Airway Epithelium as 3-D In Vitro Model for Nasal Polyposis

et al. 2014

View full text Add to dashboard Cite

BackgroundPrimary human airway epithelial cells cultured in an air-liquid interface (ALI) develop a well-differentiated epithelium. However, neither characterization of mucociliar differentiation overtime nor the inflammatory function of reconstituted nasal polyp (NP) epithelia have been described.Objectives1st) To develop and characterize the mucociliar differentiation overtime of human epithelial cells of chronic rhinosinusitis with nasal polyps (CRSwNP) in ALI culture system; 2nd) To corroborate that 3D in vitro model of NP reconstituted epithelium maintains, compared to control nasal mucosa (NM), an inflammatory function.MethodsEpithelial cells were obtained from 9 NP and 7 control NM, and differentiated in ALI culture for 28 days. Mucociliary differentiation was characterized at different times (0, 7, 14, 21, and 28 days) using ultrastructure analysis by electron microscopy; ΔNp63 (basal stem/progenitor cell), β-tubulin IV (cilia), and MUC5AC (goblet cell) expression by immunocytochemistry; and mucous (MUC5AC, MUC5B) and serous (Lactoferrin) secretion by ELISA. Inflammatory function of ALI cultures (at days 0, 14, and 28) through cytokine (IL-8, IL-1β, IL-6, IL-10, TNF-α, and IL-12p70) and chemokine (RANTES, MIG, MCP-1, IP-10, eotaxin-1, and GM-CSF) production was analysed by CBA (Cytometric Bead Array).ResultsIn both NP and control NM ALI cultures, pseudostratified epithelium with ciliated, mucus-secreting, and basal cells were observed by electron microscopy at days 14 and 28. Displaying epithelial cell re-differentation, β-tubulin IV and MUC5AC positive cells increased, while ΔNp63 positive cells decreased overtime. No significant differences were found overtime in MUC5AC, MUC5B, and lactoferrin secretions between both ALI cultures. IL-8 and GM-CSF were significantly increased in NP compared to control NM regenerated epithelia.ConclusionReconstituted epithelia from human NP epithelial cells cultured in ALI system provides a 3D in vitro model that could be useful both for studying the role of epithelium in CRSwNP while developing new therapeutic strategies, including cell therapy, for CRSwNP.

show abstract

Section: Discussionsupporting

confidence: 93%

Reconstituted Human Upper Airway Epithelium as 3-D In Vitro Model for Nasal Polyposis

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Fungal allergens also induce the production of chemokines, like IL-8, RANTES and eotaxin. These CC chemokines produced by nasal epithelial cells induce the migration of eosinophils [12]. Fungal allergens are diverse in their physiological, chemical and immunological characteristics.…”

Section: Discussionmentioning

confidence: 99%

Airborne Fungi Induce Nasal Polyp Epithelial Cell Activation and Toll-Like Receptor Expression

Shin

Lee²

2010

Int Arch Allergy Immunol

Self Cite

View full text Add to dashboard Cite

Background: The nasal epithelium is the first barrier encountered by airborne allergens and is an active participant in airway inflammation. Fungi have been increasingly recognized as important pathogens in sinusitis and airway diseases. The aim of the study was to evaluate fungal protease activity during cytokine production in nasal polyp epithelial cells and to determine the expression of Toll-like receptor (TLR) mRNA by fungi. Methods: Nasal polyp epithelial cells were obtained from patients and stimulated with Alternaria and Aspergillus. Interleukin-8 (IL-8) and granulocyte macrophage colony-stimulating factor (GM-CSF) were measured to determine the activation of epithelial cells. Reverse transcriptase polymerase chain reaction for the TLR mRNA expression of the nasal epithelial cells was performed. Cytokine production was inhibited with protease inhibitors and anti-human TLR antibodies. Results: The fungi enhanced the production of IL-8 and GM-CSF from nasal epithelial cells. When nasal epithelial cells were activated by the fungi, TLR2, TLR3 and TLR4 mRNAs were more strongly expressed than in the nonactivated cells. Cytokine production was inhibited by protease inhibitors and anti-human TLR4 antibodies. Conclusions: The results of this study showed that fungi interacted with nasal epithelial cells and enhanced the production of cytokines and TLR mRNA expression. The cytokine production was related to the protease in fungi and TLR4.

show abstract

“…Peripheral blood eosinophils have been used in some co-culture studies with primary nasal epithelial cells, mainly to evaluate the effect of AEC-soluble factors on eosinophil migration and activation, but also how eosinophil soluble factors affect nasal epithelium [178,179,180]. Similar studies with AEC-conditioned medium have also been used to investigate mast cell proliferation and one group has investigated mast cell adhesion to tracheal epithelial cells in a canine system [181,182].…”

Section: The Accompanying Co-cultured Cellsmentioning

confidence: 99%

Polarized Airway Epithelial Models for Immunological Co-Culture Studies

Papazian

Würtzen

Hansen

2016

Int Arch Allergy Immunol

View full text Add to dashboard Cite

Epithelial cells line all cavities and surfaces throughout the body and play a substantial role in maintaining tissue homeostasis. Asthma and other atopic diseases are increasing worldwide and allergic disorders are hypothesized to be a consequence of a combination of dysregulation of the epithelial response towards environmental antigens and genetic susceptibility, resulting in inflammation and T cell-derived immune responses. In vivo animal models have long been used to study immune homeostasis of the airways but are limited by species restriction and lack of exposure to a natural environment of both potential allergens and microflora. Limitations of these models prompt a need to develop new human cell-based in vitro models. A variety of co-culture systems for modelling the respiratory epithelium exist and are available to the scientific community. The models have become increasingly sophisticated and specific care needs to be taken with regard to cell types, culture medium and culture models, depending on the aim of the study. Although great strides have been made, there is still a need for further optimization, and optimally also for standardization, in order for in vitro co-culture models to become powerful tools in the discovery of key molecules dictating immunity and/or tolerance, and for understanding the complex interplay that takes place between mucosa, airway epithelium and resident or infiltrating immune cells. This review focuses on current knowledge and the advantages and limitations of the different cell types and culture methods used in co-culture models of the human airways.

show abstract

Protease-dependent activation of nasal polyp epithelial cells by airborne fungi leads to migration of eosinophils and neutrophils

Cited by 67 publications

References 17 publications

Reconstituted Human Upper Airway Epithelium as 3-D In Vitro Model for Nasal Polyposis

Reconstituted Human Upper Airway Epithelium as 3-D In Vitro Model for Nasal Polyposis

Airborne Fungi Induce Nasal Polyp Epithelial Cell Activation and Toll-Like Receptor Expression

Polarized Airway Epithelial Models for Immunological Co-Culture Studies

Contact Info

Product

Resources

About