Impaired barrier function in patients with house dust mite–induced allergic rhinitis is accompanied by decreased occludin and zonula occludens-1 expression

Steelant, Brecht; Farré, Ricard; Wawrzyniak, Paulina; Belmans, Jochen; Dekimpe, Emily; Vanheel, Hanne; Gerven, Laura Van; Krohn, Inge Kortekaas; Bullens, Dominique; Ceuppens, Jan L.; Akdiş, Cezmi A.; Boeckxstaens, Guy E.; Seys, Sven; Hellings, Peter W.

doi:10.1016/j.jaci.2015.10.050

Cited by 281 publications

(342 citation statements)

References 46 publications

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“…Early studies by Davies, Holgate, Hackett, Knight and others found evidence for persistence of EMT in asthma 120–123 , although it is more often described as a mild, “partial EMT” phenotype, which could contribute to poor expression of conventional EMT markers in asthmatic airways 32 . More recent studies found similar evidence for increased EMT in allergic rhinitis 42, 43 . Several studies have demonstrated ongoing EMT in CRS 37, 47, 49–51 .…”

Section: Mechanisms Of Barrier Defectssupporting

confidence: 55%

“…In vitro , IL-4 and TNF induced loss of these markers in epithelium. Steelant et al observed decreased barrier function measured in vitro using primary epithelial cells collected in patients with allergic rhinitis compared to healthy controls and found decreased expression of the tight junction proteins occludin and ZO-1 43 .…”

Section: Barrier Defects In Type 2 Diseasesmentioning

confidence: 99%

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

Schleimer

Berdnikovs

2017

Journal of Allergy and Clinical Immunology

141

122

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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.

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Section: Mechanisms Of Barrier Defectssupporting

confidence: 55%

Section: Barrier Defects In Type 2 Diseasesmentioning

confidence: 99%

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

Schleimer

Berdnikovs

2017

Journal of Allergy and Clinical Immunology

141

122

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“…Lee et al reported decreased ZO-1 and E-cadherin expression in the nasal epithelium of patients with AR 20 . Consistent with these findings, Steelant et al reported decreased ZO-1 and occludin expression as assessed by RT-qPCR and weak immunofluorescent staining in AR biopsy specimens 21 .…”

Section: Epithelial Barrier Function In Atopic Diseasesupporting

confidence: 52%

“…Steelant et al have also investigated the functional consequences of barrier dysfunction in symptomatic AR 21 . To do so, they first obtained nasal biopsy specimens from control and house-dust mite (HDM)-AR patients.…”

Section: Epithelial Barrier Function In Atopic Diseasementioning

confidence: 99%

The Role of the Sinonasal Epithelium in Allergic Rhinitis

London¹,

Ramanathan²

2017

Otolaryngologic Clinics of North America

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Synopsis The sinonasal epithelial barrier is comprised of tight and adherens junction proteins. Disruption of epithelial barrier function has been hypothesized to contribute to allergic disease such as allergic rhinitis through increased passage of antigens and exposure of underlying tissue to these stimuli. Several mechanisms of sinonasal epithelial barrier disruption include antigen proteolytic activity, inflammatory cytokine-mediated tight junction breakdown, or exacerbation from environmental stimuli. Mechanisms of sinonasal epithelial barrier stabilization include corticosteroids and nuclear erythroid 2–related factor 2 (Nrf2) cytoprotective pathway activation. Additional studies will aid in determining the contribution of epithelial barrier function in allergic rhinitis pathophysiology and treatment.

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“…It not only largely affects social life, sleep and work, but also increases family and socioeconomic burden [1]. Despite rapid progress in the treatment of AR, such as immunotherapy, intranasal steroids, and antihistamines, 20% of AR patients already do not show sufficient subjective and objective improvement [3]. Accordingly, it is of foremost importance to develop potential pharmacological agents for the treatment of AR.…”

Section: Introductionmentioning

confidence: 99%

MicroRNA-133b Ameliorates Allergic Inflammation and Symptom in Murine Model of Allergic Rhinitis by Targeting Nlrp3

Xiao¹,

Jiang²,

Hu³

et al. 2017

Cell Physiol Biochem

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Background: Emerging evidences indicate that post-transcriptional regulation by microRNAs is critical in allergic rhinitis (AR) pathogenesis. MircroRNA-133b (miR-133b) was recently suggested as a potential predictor of AR. However, the in vivo effect of miR-133b on AR is unclear. Methods: AR model was established in BALB/c mice by intraperitoneal sensitization and intranasal challenge with ovalbumin (OVA). MiR-133b agomir was then intranasally administrated to mice after OVA challenge for another 7 days. The symptom of nasal rubbing and sneezing were recorded after the last OVA challenge. Nasal mucosa tissues and serum were collected. MiR-133b expression, serum OVA-specific immunoglobulin E (IgE) concentration, proinflammatory cytokines (TNF-α, IL-4, IL-5, IL-10 and IFN-γ) levels, and Nlrp3 inflammasome activation were measured by RT-PCR, ELISA, western blotting or immunohistochemistry, respectively. Histopathologic changes were evaluated using hematoxylin and eosin and Sirius red staining. The luciferase activity and protein expression of Nlrp3 were also determined. Results: MiR-133b expression was significantly decreased in nasal mucosa of AR mice, which was restored by nasal administration with miR-133b agomir. Upregulation of miR-133b markedly reduced the concentration of OVA-specific IgE, the frequencies of nasal rubbing and sneezing, and the levels of cytokines (TNF-α, IL-4, IL-5 and IFN-γ). Levels of IL-4, IL-5, IL-10 and IFN-γ produced by cervical lymph node cells were significantly lowered in miR-133b agomir-treated mice. Moreover, miR-133b also appeared to strongly attenuate pathological alterations and eosinophils and mast cells infiltration in nasal mucosa. Notably, we demonstrated for the first time that miR-133b negatively regulated Nlrp3 expression through binding with the 3’ untranslated region of Nlrp3. Consequently, infection of miR-133b in nasal mucosa remarkably suppressed the Nlrp3 inflammasome activation, as evidenced by reduced Nlrp3, Caspase-1, ASC, IL-18 and IL-1 expressions. Conclusion: MiR-133b alleviates allergic symptom in AR mice by inhibition of Nlrp3 inflammasome-meditated inflammation. These findings provide us an insight into the potential role of miR-133b in relation to AR treatment.

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Impaired barrier function in patients with house dust mite–induced allergic rhinitis is accompanied by decreased occludin and zonula occludens-1 expression

Cited by 281 publications

References 46 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

The Role of the Sinonasal Epithelium in Allergic Rhinitis

MicroRNA-133b Ameliorates Allergic Inflammation and Symptom in Murine Model of Allergic Rhinitis by Targeting Nlrp3

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