Effects of chronic exposure to<i>Aspergillus fumigatus</i>on epidermal growth factor receptor expression in the airway epithelial cells of asthmatic rats

Gao, Furong; Cao, Tong-Mei; Gao, Yanyan; Liu, Meijuan; Liu, Yong-Quan; Wang, Ze

doi:10.3109/01902148.2014.918212

Cited by 7 publications

(13 citation statements)

References 24 publications

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“…1d–f). EGF is relatively well studied in asthma pathogenesis, including fungal asthma, where experimental models of Alternaria 15 and Aspergillus 16 have documented upregulation of the EGF receptor and its various ligands. The observation of high IL-1RA levels negatively correlating with PC20 is intriguing and one we are currently pursuing (Godwin and Steele, manuscript in preparation).…”

Section: Resultsmentioning

confidence: 99%

The common γ-chain cytokine IL-7 promotes immunopathogenesis during fungal asthma

et al. 2018

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Asthmatics sensitized to fungi are reported to have more severe asthma, yet the immunopathogenic pathways contributing to this severity have not been identified. In a pilot assessment of human asthmatics, those subjects sensitized to fungi demonstrated elevated levels of the common γ-chain cytokine IL-7 in lung lavage fluid, which negatively correlated with the lung function measurement PC20. Subsequently, we show that IL-7 administration during experimental fungal asthma worsened lung function and increased the levels of type 2 cytokines (IL-4, IL-5, IL-13), proallergic chemokines (CCL17, CCL22) and proinflammatory cytokines (IL-1α, IL-1β). Intriguingly, IL-7 administration also increased IL-22, which we have previously reported to drive immunopathogenic responses in experimental fungal asthma. Employing IL22R26R reporter mice, we identified γδ T cells, iNKT cells, CD4 T cells and ILC3s as sources of IL-22 during fungal asthma; however, only iNKT cells were significantly increased after IL-7 administration. IL-7-induced immunopathogenesis required both type 2 and IL-22 responses. Blockade of IL-7Rα in vivo resulted in attenuated IL-22 production, lower CCL22 levels, decreased iNKT cell, CD4 T-cell and eosinophil recruitment, yet paradoxically increased dynamic lung resistance. Collectively, these results suggest a complex role for IL-7 signaling in allergic fungal asthma.

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Section: Resultsmentioning

confidence: 99%

The common γ-chain cytokine IL-7 promotes immunopathogenesis during fungal asthma

et al. 2018

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“…Fungi are commonly found in the nasal mucosa and relatively few species are implicated in airway inflammatory disease. Alternaria and Aspergillus are known common pathogens found in nasal secretion and they induce the production of chemical mediators from nasal epithelial cells and fibroblasts [ 3 , 4 ]. TLR2, TLR4, and TLR5 seem to be important pattern recognition receptors for fungi [ 3 , 5 ].…”

Section: Introductionmentioning

confidence: 99%

The Effects of Melittin and Apamin on Airborne Fungi-Induced Chemical Mediator and Extracellular Matrix Production from Nasal Polyp Fibroblasts

Shin

Choi

et al. 2017

Toxins

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Melittin and apamin are the main components of bee venom and they have been known to have anti-inflammatory and anti-fibrotic properties. The aim of this study was to evaluate the effect of melittin and apamin on airborne fungi-induced chemical mediator and extracellular matrix (ECM) production in nasal fibroblasts. Primary nasal fibroblasts were isolated from nasal polyps, which were collected during endoscopic sinus surgery. Nasal fibroblasts were treated with Alternaria and Aspergillus. The effects of melittin and apamin on the production of interleukin (IL)-6 and IL-8 were determined with enzyme linked immunosorbent assay. ECM mRNA and protein expressions were determined with the use of quantitative RT-PCR and Western blot. Alternaria-induced IL-6 and IL-8 production was significantly inhibited by apamin. However, melittin did not influence the production of IL-6 and IL-8 from nasal fibroblasts. Melittin or apamin significantly inhibited collagen type I, TIMP-1, and MMP-9 mRNA expression and protein production from nasal fibroblasts. Melittin and apamin inhibited Alternaria-induced phosphorylation of Smad 2/3 and p38 MAPK. Melittin and apamin can inhibit the fungi-induced production of chemical mediators and ECM from nasal fibroblasts. These results suggest the possible role of melittin and apamin in the treatment of fungi induced airway inflammatory diseases.

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“…A role for the epidermal growth factor receptor (EGFR) pathway in fungal allergy was supported in 6 (10%) of the studies 45,49,55,75,81,91 . The EGFR pathway plays a role in mucin production, airway epithelial repair and airway remodelling in response to disruption or injury to the epithelial layer 102–105 .…”

Section: Discussionmentioning

confidence: 99%

“…EGFR is a transmembrane tyrosine kinase that is activated by several ligands, including epidermal growth factor (EGF), heparin‐binding EGF (hb‐EGF), transforming growth factor α (TGF‐α) and amphiregulin 102,103,111 . An increased level of both EGF and TGF‐α was observed in the bronchoalveolar lavage fluid (BALF) of rats exposed to A. fumigatus spores, with increasing levels of EGF and TGF‐α corresponding to prolonged spore exposure 49 . EGFR ligands are formed as pro‐ligands or transmembrane precursors and are cleaved by proteases, namely MMPs and ‘a disentegrin and metalloprotease’ (ADAM) proteases, to release the mature ligand 102,105,108 .…”

Section: Discussionmentioning

confidence: 99%

A scoping review: What are the cellular mechanisms that drive the allergic inflammatory response to fungal allergens in the lung epithelium?

Goode¹,

Marczylo²

2023

Clinical & Translational All

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Allergic airway disease (AAD) is a collective term for respiratory disorders that can be exacerbated upon exposure to airborne allergens. The contribution of fungal allergens to AAD has become well established over recent years. We conducted a comprehensive review of the literature using Preferred Reporting Items for Systematic Reviews and Meta‐Analyses guidelines to better understand the mechanisms involved in the allergic response to fungi in airway epithelia, identify knowledge gaps and make recommendations for future research. The search resulted in 61 studies for final analysis. Despite heterogeneity in the models and methods used, we identified major pathways involved in fungal allergy. These included the activation of protease‐activated receptor 2, the EGFR pathway, adenosine triphosphate and purinergic receptor‐dependent release of IL33, and oxidative stress, which drove mucin expression and goblet cell metaplasia, Th2 cytokine production, reduced barrier integrity, eosinophil recruitment, and airway hyperresponsiveness. However, there were several knowledge gaps and therefore we recommend future research should focus on the use of more physiologically relevant methods to directly compare key allergenic fungal species, clarify specific mechanisms of fungal allergy, and assess the fungal allergy in disease models. This will inform disease management and future interventions, ultimately reducing the burden of disease.

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Effects of chronic exposure toAspergillus fumigatuson epidermal growth factor receptor expression in the airway epithelial cells of asthmatic rats

Cited by 7 publications

References 24 publications

The common γ-chain cytokine IL-7 promotes immunopathogenesis during fungal asthma

The common γ-chain cytokine IL-7 promotes immunopathogenesis during fungal asthma

The Effects of Melittin and Apamin on Airborne Fungi-Induced Chemical Mediator and Extracellular Matrix Production from Nasal Polyp Fibroblasts

A scoping review: What are the cellular mechanisms that drive the allergic inflammatory response to fungal allergens in the lung epithelium?

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