Expression of protease‐activated receptors in allergic fungal rhinosinusitis

Ebert, Charles S.; McKinney, Kibwei A.; Urrutia, Gene; Wu, Michael C.; Rose, Austin S.; Fleischman, Gita M.; Thorp, Brian D.; Senior, Brent A.; Zanation, Adam M.

doi:10.1002/alr.21295

Cited by 19 publications

(16 citation statements)

References 45 publications

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“…Unlike ovalbumin typically used, our study utilized cockroach antigen capable of activating protease-activated receptors (46). Protease-activated receptors enhance production of inflammatory cytokines and potentiate Th2 type responses (47). The model allergen may affect the role of Treg cells during allergic inflammation.…”

Section: Discussionmentioning

confidence: 99%

Lung-Infiltrating Foxp3+ Regulatory T Cells Are Quantitatively and Qualitatively Different during Eosinophilic and Neutrophilic Allergic Airway Inflammation but Essential To Control the Inflammation

Jang

Nguyen

Kim

et al. 2017

The Journal of Immunology

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Understanding functions of Foxp3+ regulatory T (Treg) cells during allergic airway inflammation remains incomplete. In this study, we report that during cockroach antigen (CA)-induced allergic airway inflammation Foxp3+ Treg cells are rapidly mobilized into the inflamed lung tissues. However, the level of Treg cell accumulation in the lung was different depending on the type of inflammation. During eosinophilic airway inflammation, ~30% of lung infiltrating CD4 T cells express Foxp3, an indicative of Treg cells. On the contrary, only ~10% of infiltrating CD4 T cells express Foxp3 during neutrophilic airway inflammation. Despite the different accumulation, both the lung inflammation and inflammatory T cell responses were aggravated following Treg cell depletion regardless of the type of inflammation, suggesting regulatory roles of Treg cells. Interestingly, however, the extent to which inflammatory responses are aggravated by Treg cell depletion was significantly greater during eosinophilic airway inflammation. Indeed, lung infiltrating Treg cells exhibit phenotypic and functional features associated with potent suppression. Our results demonstrate that Treg cells are essential regulators of inflammation regardless of the type of inflammation, although the mechanisms employed by Treg cells to control inflammation may be shaped by environmental cues available to those Treg cells.

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Section: Discussionmentioning

confidence: 99%

Lung-Infiltrating Foxp3+ Regulatory T Cells Are Quantitatively and Qualitatively Different during Eosinophilic and Neutrophilic Allergic Airway Inflammation but Essential To Control the Inflammation

Jang

Nguyen

Kim

et al. 2017

The Journal of Immunology

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“…426 Additionally, genetic analysis has demonstrated differential gene expression and allelic variations in AFRS vs other CRS subtypes. 634,1095,1096 A local mucosal response also likely contributes to AFRS pathogenesis. Respiratory epithelial cells can initiate a local Th2 immune response.…”

Section: Viiig Crswnp and Afrs: Differences In Pathophysiologymentioning

confidence: 99%

International Consensus Statement on Allergy and Rhinology: Rhinosinusitis

Orlandi

Kingdom

Hwang

et al. 2016

Int Forum Allergy Rhinol

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554

888

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Background:The body of knowledge regarding rhinosinusitis (RS) continues to expand, with rapid growth in number of publications, yet substantial variability in the quality of those presentations. In an effort to both consolidate and critically appraise this information, rhinologic experts from around the world have produced the International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR:RS). Methods:Evidence-based reviews with recommendations (EBRRs) were developed for scores of topics, using previously reported methodology. Where existing evidence was insufficient for an EBRR, an evidence-based review (EBR) was produced. The sections were then synthesized and the entire manuscript was then reviewed by all authors for consensus. Results:The resulting ICAR:RS document addresses multiple topics in RS, including acute RS (ARS), chronic RS (CRS) with and without nasal polyps (CRSwNP and CRSsNP), recurrent acute RS (RARS), acute exacerbation of CRS (AE-CRS), and pediatric RS. Conclusion:As a critical review of the RS literature, ICAR:RS provides a thorough review of pathophysiology and evidence-based recommendations for medical and surgical treatment. It also demonstrates the significant gaps in our understanding of the pathophysiology and optimal management of RS. Too o en the foundation upon which these recommendations are based is comprised of lowerlevel evidence. It is our hope that this summary of the evidence in RS will point out where additional research efforts may be directed. C 2016 ARS-AAOA, LLC. Key Words:rhinosinusitis; chronic rhinosinusitis; acute rhinosinusitis; recurrent acute rhinosinusitis; evidence-based medicine; systematic review; endoscopic sinus surgery List of Abbreviations Used

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“…PAR-2 is highly expressed in airway tissues and airway cell lines, such as A549 and 16HBE14o2 (16HBE) cells (6), and in primary nasal cells (7). The regulation of PAR-2 expression is poorly understood; PAR-2 mRNA is upregulated in allergic rhinitis nasal samples (8), although others found no alteration of PAR-2 expression in patients with allergic fungal rhinosinusitis (9). PAR-2 has multiple known effects, including activating fluid secretion from airway submucosal glands of mouse trachea (10) and from human inferior turbinate explants (11).…”

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confidence: 99%

Protease‐activated receptor 2 activates airway apical membrane chloride permeability and increases ciliary beating

et al. 2017

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Mucociliary clearance, driven by the engine of ciliary beating, is the primary physical airway defense against inhaled pathogens and irritants. A better understanding of the regulation of ciliary beating and mucociliary transport is necessary for identifying new receptor targets to stimulate improved clearance in airway diseases, such as cystic fibrosis and chronic rhinosinusitis. In this study, we examined the protease-activated receptor (PAR)-2, a GPCR previously shown to regulate airway cell cytokine and mucus secretion, and transepithelial Cl current. PAR-2 is activated by proteases secreted by airway neutrophils and pathogens. We cultured various airway cell lines, primary human and mouse sinonasal cells, and human bronchial cells at air-liquid interface and examined them using molecular biology, biochemistry, and live-cell imaging. We found that PAR-2 is expressed basolaterally, where it stimulates both intracellular Ca release and Ca influx, which activates low-level nitric oxide production, increases apical membrane Cl permeability ∼3-5-fold, and increases ciliary beating ∼20-50%. No molecular or functional evidence of PAR-4 was observed. These data suggest a novel and previously overlooked role of PAR-2 in airway physiology, adding to our understanding of the role of this receptor in airway Ca signaling and innate immunity.-McMahon, D. B., Workman, A. D., Kohanski, M. A., Carey, R. M., Freund, J. R., Hariri, B. M., Chen, B., Doghramji, L. J., Adappa, N. D., Palmer, J. N., Kennedy, D. W., Lee, R. J. Protease-activated receptor 2 activates airway apical membrane chloride permeability and increases ciliary beating.

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Expression of protease‐activated receptors in allergic fungal rhinosinusitis

Abstract: PARs have been shown to enhance production of inflammatory cytokines and potentiate Th2 responses. In this initial report, patients with AFRS have a significantly increased expression of PAR3 compared to nondiseased controls.

Cited by 19 publications

References 45 publications

Lung-Infiltrating Foxp3+ Regulatory T Cells Are Quantitatively and Qualitatively Different during Eosinophilic and Neutrophilic Allergic Airway Inflammation but Essential To Control the Inflammation

Lung-Infiltrating Foxp3+ Regulatory T Cells Are Quantitatively and Qualitatively Different during Eosinophilic and Neutrophilic Allergic Airway Inflammation but Essential To Control the Inflammation

International Consensus Statement on Allergy and Rhinology: Rhinosinusitis

Protease‐activated receptor 2 activates airway apical membrane chloride permeability and increases ciliary beating

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