Epithelial tight junction alterations in nasal polyposis

Rogers, G. Aaron; Beste, Kyle A. Den; Parkos, Charles A.; Nusrat, Asma; DelGaudio, John M.; Wise, Sarah K.

doi:10.1002/alr.20014

Cited by 57 publications

(60 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Epithelial damage, including shortening of desmosomes, was reported by Shahana et al in a study using electron microscopy in polyp tissue derived from asthmatic patients 49 . Reductions of the tight junction proteins claudin-1 and occludin in CRS tissues were reported in another study 50 . The group of Bachert reported that ZO-1, occludin and E-cadherin were all reduced in mature polyps removed from CRSwNP patients 51 .…”

Section: Barrier Defects In Type 2 Diseasessupporting

confidence: 54%

Etiology of epithelial barrier dysfunction in patients with type 2 inflammatory diseases

Schleimer

Berdnikovs

2017

Journal of Allergy and Clinical Immunology

143

122

View full text Add to dashboard Cite

Epithelial barriers of the skin, gastrointestinal tract and airway serve common critical functions such as maintaining a physical barrier against environmental insults and allergens, as well as providing a tissue interface balancing the communication between the internal and external environments. We now understand that in allergic disease, regardless of tissue location, the homeostatic balance of the epithelial barrier is skewed towards loss of differentiation, reduced junctional integrity and impaired innate defense. Importantly, epithelial dysfunction characterized by these traits appears to pre-date atopy and development of allergic disease. Despite our growing appreciation of the centrality of barrier dysfunction in the initiation of allergic disease, many important questions remain to be answered regarding the mechanisms disrupting the normal barrier function. Although our external environment (proteases, allergens, injury) is classically thought of as a principal contributor to barrier disruption associated with allergic sensitization, there is a need to better understand contributions of the internal environment (hormones, diet, circadian clock). Systemic drivers of disease, such as alterations of the endocrine system, metabolism and aberrant control of developmental signaling, are emerging as new players in driving epithelial dysfunction and allergic predisposition at various barrier sites. Identifying such central mediators of epithelial dysfunction, using both systems biology tools and causality-driven laboratory experimentation, will be essential in building new strategic interventions to prevent or reverse the process of barrier loss in allergy.

show abstract

Section: Barrier Defects In Type 2 Diseasessupporting

confidence: 54%

Etiology of epithelial barrier dysfunction in patients with type 2 inflammatory diseases

Schleimer

Berdnikovs

2017

Journal of Allergy and Clinical Immunology

143

122

View full text Add to dashboard Cite

show abstract

“…497 The barrier is maintained via ongoing production of AJC proteins as well as protective antiprotease molecules. The polypoid form of CRS and a Th2 cytokine milieu have been associated with significantly decreased levels of AJC proteins [498][499][500][501] as well as diminished intrinsic protective antiprotease activity. 486,502 Functional studies have also documented increased barrier permeability in CRSwNP.…”

Section: Discussionmentioning

confidence: 99%

International Consensus Statement on Allergy and Rhinology: Rhinosinusitis

Orlandi

Kingdom

Hwang

et al. 2016

Int Forum Allergy Rhinol

558

888

View full text Add to dashboard Cite

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

show abstract

“…Instead, the higher glucose concentrations in nasal secretions from patients with CRS likely derives from the sera via epithelial transudate/exudate leaking through the epithelial barrier due to chronic infection/inflammation and epithelial damage that varies with individual patient disease (46). Supporting this, proinflammatory mediators have been shown in vitro to increase paracellular glucose flux in human bronchial cell monolayers (52) and disrupt tight junctions in human sinonasal epithelial cultures (53,54).…”

Section: Figurementioning

confidence: 99%

Bitter and sweet taste receptors regulate human upper respiratory innate immunity

Lee¹,

Kofonow²,

Rosen³

et al. 2014

J. Clin. Invest.

365

639

View full text Add to dashboard Cite

Bitter taste receptors (T2Rs) in the human airway detect harmful compounds, including secreted bacterial products. Here, using human primary sinonasal air-liquid interface cultures and tissue explants, we determined that activation of a subset of airway T2Rs expressed in nasal solitary chemosensory cells activates a calcium wave that propagates through gap junctions to the surrounding respiratory epithelial cells. The T2R-dependent calcium wave stimulated robust secretion of antimicrobial peptides into the mucus that was capable of killing a variety of respiratory pathogens. Furthermore, sweet taste receptor (T1R2/3) activation suppressed T2R-mediated antimicrobial peptide secretion, suggesting that T1R2/3-mediated inhibition of T2Rs prevents full antimicrobial peptide release during times of relative health. In contrast, during acute bacterial infection, T1R2/3 is likely deactivated in response to bacterial consumption of airway surface liquid glucose, alleviating T2R inhibition and resulting in antimicrobial peptide secretion. We found that patients with chronic rhinosinusitis have elevated glucose concentrations in their nasal secretions, and other reports have shown that patients with hyperglycemia likewise have elevated nasal glucose levels. These data suggest that increased glucose in respiratory secretions in pathologic states, such as chronic rhinosinusitis or hyperglycemia, promotes tonic activation of T1R2/3 and suppresses T2R-mediated innate defense. Furthermore, targeting T1R2/3-dependent suppression of T2Rs may have therapeutic potential for upper respiratory tract infections.

show abstract

Epithelial tight junction alterations in nasal polyposis

Cited by 57 publications

References 19 publications

Etiology of epithelial barrier dysfunction in patients with type 2 inflammatory diseases

Etiology of epithelial barrier dysfunction in patients with type 2 inflammatory diseases

International Consensus Statement on Allergy and Rhinology: Rhinosinusitis

Bitter and sweet taste receptors regulate human upper respiratory innate immunity

Contact Info

Product

Resources

About