Nasal Epithelial Barrier Integrity and Tight Junctions Disruption in Allergic Rhinitis: Overview and Pathogenic Insights.
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ABSTRACT:
SUBMITTER: Nur Husna SM
PROVIDER: S-EPMC8176953 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Allergic rhinitis (AR) is a common disease affecting 400 million of the population worldwide. Nasal epithelial cells form a barrier against the invasion of environmental pathogens. These nasal epithelial cells are connected together by tight junction (TJ) proteins including zonula occludens-1 (ZO-1), ZO-2 and ZO-3. Impairment of ZO proteins are observed in AR patients whereby dysfunction of ZOs allows allergens to pass the nasal passage into the subepithelium causing AR development. In this review, we discuss ZO proteins and their impairment leading to AR, regulation of their expression by Th1 cytokines (i.e., IL-2, TNF-? and IFN-?), Th2 cytokines (i.e., IL-4 and IL-13) and histone deacetylases (i.e., HDAC1 and HDAC2). These findings are pivotal for future development of targeted therapies by restoring ZO protein expression and improving nasal epithelial barrier integrity in AR patients.
| S-EPMC7476493 | biostudies-literature
Project description:PurposeThe prevalence of "ocal allergic rhinitis" within individuals suffering from perennial rhinitis remains uncertain, and patients usually are diagnosed with non-allergic rhinitis. The aim of this study was to evaluate the prevalence of a potential "local allergic rhinitis" in subjects suffering from non-allergic rhinitis in a non-selected group of young students.Methods131 students (age 25.0 ± 5.1 years) with a possible allergic rhinitis and 25 non-allergic controls without rhinitis symptoms (age 22.0 ± 2.0 years) were recruited by public postings. 97 of 131 students with rhinitis were tested positive (≥3 mm) to prick testing with 17 frequent allergens at visit 1. Twenty-four 24 subjects with a house dust mite allergy, 21 subjects with a non-allergic rhinitis, and 18 non-allergic controls were further investigated at visit 2. Blood samples were taken, and nasal secretion was examined. In addition, all groups performed a nasal provocation test with house dust mite (HDM).ResultsIn serum and nasal secretion, total IgE and house dust mite specific IgE significantly differed between HDM positive subjects and controls. However, no differences between non-allergic subjects and control subjects were quantifiable. Neither a nasal provocation test nor a nasal IgE to HDM allergens showed a measurable positive response in any of the non-allergic rhinitis subjects as well as the healthy controls, whilst being positive in 13 subjects with HDM allergy.ConclusionsNasal IgE is present in subjects with HDM allergy, but not in non-allergic rhinitis. In the investigated non-selected population, exclusive local production of IgE is absent. By implication, therefore, our findings challenge the emerging concept of local allergic rhinitis.Study identifier at ClinicalTrials.gov: NCT02810535.
| S-EPMC7322186 | biostudies-literature
Project description:IntroductionAlthough recent studies have shown that the human microbiome is involved in the pathogenesis of allergic diseases, the impact of microbiota on allergic rhinitis (AR) and non-allergic rhinitis (nAR) has not been elucidated. The aim of this study was to investigate the differences in the composition of the nasal flora in patients with AR and nAR and their role in the pathogenesis.MethodFrom February to September 2022, 35 AR patients and 35 nAR patients admitted to Harbin Medical University's Second Affiliated Hospital, as well as 20 healthy subjects who underwent physical examination during the same period, were subjected to 16SrDNA and metagenomic sequencing of nasal flora.ResultsThe microbiota composition of the three groups of study subjects differs significantly. The relative abundance of Vibrio vulnificus and Acinetobacter baumanni in the nasal cavity of AR patients was significantly higher when compared to nAR patients, while the relative abundance of Lactobacillus murinus, Lactobacillus iners, Proteobacteria, Pseudomonadales, and Escherichia coli was lower. In addition, Lactobacillus murinus and Lacttobacillus kunkeei were also negatively correlated with IgE, while Lacttobacillus kunkeei was positively correlated with age. The relative distribution of Faecalibacterium was higher in moderate than in severe AR patients. According to KEGG functional enrichment annotation, ICMT(protein-S-isoprenylcysteine O-methyltransferase,ICMT) is an AR microbiota-specific enzyme that plays a role, while glycan biosynthesis and metabolism are more active in AR microbiota. For AR, the model containing Parabacteroides goldstemii, Sutterella-SP-6FBBBBH3, Pseudoalteromonas luteoviolacea, Lachnospiraceae bacterium-615, and Bacteroides coprocola had the highest the area under the curve (AUC), which was 0.9733(95%CI:0.926-1.000) in the constructed random forest prediction model. The largest AUC for nAR is 0.984(95%CI:0.949-1.000) for the model containing Pseudomonas-SP-LTJR-52, Lachnospiraceae bacterium-615, Prevotella corporis, Anaerococcus vaginalis, and Roseburia inulinivorans.ConclusionIn conclusion, patients with AR and nAR had significantly different microbiota profiles compared to healthy controls. The results suggest that the nasal microbiota may play a key role in the pathogenesis and symptoms of AR and nAR, providing us with new ideas for the treatment of AR and nAR.
| S-EPMC10166850 | biostudies-literature
Project description:Allergic rhinitis is one of the most common diseases, which is caused by IgE-mediated reactions to inhaled allergens. Essential oils from the Mentha piperita leaf (EOM) are known to be effective for various diseases, such as respiratory diseases. However, the effect of inhalation of EOM on tight junctions and inflammation related to allergic rhinitis is not yet known. The purpose of this research was to explain the effects of the inhalation of EOM on tight junctions and inflammation of allergic rhinitis through network pharmacology and an experimental study. For that purpose, a pharmacology network analysis was conducted comprising major components of EOM. Based on the network pharmacology prediction results, we evaluated the effect of EOM on histological changes in mice with ovalbumin and PM10-induced allergic rhinitis. Allergic symptoms, infiltration of inflammatory cells, and regulation of ZO-1 were investigated in mice with allergic rhinitis. Other allergic parameters were also analyzed by reverse transcription polymerase chain reaction and western blot in nasal epithelial cells. In the network analysis, the effects of EOM were closely related to tight junctions and inflammation in allergic rhinitis. Consistent with the results from the network analysis, EOM significantly decreased epithelial thickness, mast cell degranulation, goblet cell secretion, and the infiltration of inflammatory cells in nasal tissue. EOM also regulated the MAPK-NF-κB signaling pathway, which was related to tight junctions in nasal epithelial cells. This research confirmed that inhalation of EOM effectively restores tight junctions and suppresses inflammation in the allergic rhinitis model. These results reveal that EOM has a therapeutic mechanism to treat allergic rhinitis.
| S-EPMC9790934 | biostudies-literature
Project description:Meningitis induced by Pasteurella multocida has been substantially described in clinical practice in both human and veterinary medicine, but the underlying mechanisms have not been previously reported. In this study, we investigated the influence of P. multocida infection on the permeability of the blood-brain barrier (BBB) using different models. Our in vivo tests in a mouse model and in vitro tests using human brain microvascular endothelial cell (hBMEC) model showed that P. multocida infection increased murine BBB permeability in mice and hBMEC monolayer permeability. Furthermore, we observed that P. multocida infection resulted in decreased expression of tight junctions (ZO1, claudin-5, occludin) and adherens junctions (E-cadherin) between neighboring hBMECs. Subsequent experiments revealed that P. multocida infection promoted the activation of hypoxia inducible factor-1α (HIF-1α)/vascular endothelial growth factor A (VEGFA) signaling and NF-κB signaling, and suppressed the HIF-1α/VEGFA significantly remitted the decrease in ZO1/E-cadherin induced by P. multocida infection (P < 0.001). NF-κB signaling was found to contribute to the production of chemokines such as TNF-1α, IL-β, and IL-6. Additionally, transmission electron microscopy revealed that paracellular migration might be the strategy employed by P. multocida to cross the BBB. This study provides the first evidence of the migration strategy used by P. multocida to traverse the mammalian BBB. The data presented herein will contribute to a better understanding of the pathogenesis of the zoonotic pathogen P. multocida.
| S-EPMC11363436 | biostudies-literature
Project description:Tight junction defects (TJ) have been associated with a defective epithelial barrier function in allergic rhinitis (AR). Intranasal corticosteroids are potent drugs frequently used to treat AR and are shown to restore epithelial integrity by acting on TJs and by reducing type 2 cytokine production. However, the effect of different classes of intranasal corticosteroids on the epithelial barrier has not been studied. Therefore, we compared the effect of 2 intranasal corticosteroids, ie, fluticasone furoate (FF) and mometasone furoate (MF) on epithelial barrier function. Both FF and MF similarly increased trans-epithelial electrical resistance of primary nasal epithelial cell cultures from AR patients. In a house dust mite-induced allergic asthma mouse model, FF and MF had similar beneficial effects on fluorescein isothiocyanate-dextran 4 kDa mucosal permeability, eosinophilic infiltration and IL-13 levels. Both molecules increased mRNA expression of the TJ proteins occludin and zonula occludens-1, thereby restoring epithelial barrier function. Lastly, we showed that long-term FF treatment also increased expression of occludin in AR patients compared to controls. In conclusion, both FF and MF effectively restore epithelial barrier function by increasing expression of TJ proteins in AR patients.
| S-EPMC8436167 | biostudies-literature
Project description:Pulmonary pathologies including adult respiratory distress syndrome are characterized by disruption of pulmonary integrity and edema compromising respiratory function. Sphingosine 1-phosphate (S1P) is a lipid mediator synthesized and/or stored in mast cells, platelets, and epithelial cells, with production up-regulated by the proinflammatory cytokines IL-1 and TNF. S1P administration via the airways but not via the vasculature induces lung leakage. Using receptor-null mice, we show that S1P, acting on S1P3 receptor expressed on both type I and type II alveolar epithelial cells but not vascular endothelium, induces pulmonary edema by acute tight junction opening. WT but not S1P3-null mice showed disruption of pulmonary epithelial tight junctions and the appearance of paracellular gaps between epithelial cells by electron microscopy within 1 h of airways exposure to S1P. We further show by fluorescence microscopy that S1P induced rapid loss of ZO-1 reactivity, an essential component of the cytoplasmic plaque associated with tight junctions, as well as of the tetraspannin Claudin-18, an integral membrane organizer of tight junctions. S1P shows synergistic activity with the proinflammatory cytokine TNF, showing both pulmonary edema and mortality at subthreshold S1P doses. Specifically, preexposure of mice to subthreshold doses of TNF, which alone induced no lung edema, exacerbated S1P-induced edema and impaired survival. S1P, acting through S1P3, regulates epithelial integrity and acts additively with TNF in compromising respiratory barrier function. Because S1P3-null mice are resistant to S1P-induced pulmonary leakage, either alone or in the presence of TNF, S1P3 antagonism may be useful in protecting epithelial integrity in pulmonary disease.
| S-EPMC1166603 | biostudies-literature
Project description:SARS-CoV-2 has been reported to show a capacity for invading the brains of humans and model animals. However, it remains unclear whether and how SARS-CoV-2 crosses the blood-brain barrier (BBB). Herein, SARS-CoV-2 RNA was occasionally detected in the vascular wall and perivascular space, as well as in brain microvascular endothelial cells (BMECs) in the infected K18-hACE2 transgenic mice. Moreover, the permeability of the infected vessel was increased. Furthermore, disintegrity of BBB was discovered in the infected hamsters by administration of Evans blue. Interestingly, the expression of claudin5, ZO-1, occludin and the ultrastructure of tight junctions (TJs) showed unchanged, whereas, the basement membrane was disrupted in the infected animals. Using an in vitro BBB model that comprises primary BMECs with astrocytes, SARS-CoV-2 was found to infect and cross through the BMECs. Consistent with in vivo experiments, the expression of MMP9 was increased and collagen IV was decreased while the markers for TJs were not altered in the SARS-CoV-2-infected BMECs. Besides, inflammatory responses including vasculitis, glial activation, and upregulated inflammatory factors occurred after SARS-CoV-2 infection. Overall, our results provide evidence supporting that SARS-CoV-2 can cross the BBB in a transcellular pathway accompanied with basement membrane disrupted without obvious alteration of TJs.
| S-EPMC8419672 | biostudies-literature
Project description:PurposeNasal cytology is important in the diagnosis and treatment of nasal inflammatory diseases. Treatment of allergic rhinitis (AR) according to nasal cytology has not been fully studied. We plan to explore the individualized treatment of AR according to nasal cytology.MethodsNasal cytology from 468 AR patients was examined for inflammatory cell quantity (grade 0-5) and the percentage of neutrophils and eosinophils. Results were subdivided into the following categories: AR(Eos), eosinophil ≥50% of the whole inflammatory cells; AR(Neu), neutrophils ≥90%; AR(Eos/Neu), 10%≤ eosinophil <50%; AR(Low), grade 0/1 inflammatory cell quantity. Nasal cytology-guided treatment was implemented: all AR(Eos) patients (n=22) and half of the AR(Neu) patients (AR[Neu1], n=22) were treated with mometasone furoate spray and oral loratadine. Another half of the AR(Neu) patients (AR[Neu2], n=22) were treated with oral clarithromycin. Visual analog scale (VAS), symptom scores, and nasal cytology were evaluated 2 weeks before and after treatment.ResultsThere were 224/468 (47.86%) AR(Eos), 67/468 (14.32%) AR(Neu), 112/468 (23.93%) AR(Eos/Neu), and 65/468 (13.89%) AR(Low) of the AR patients studied. There were no significant differences in clinical characteristics among these subgroups, except that the nasal blockage score was higher in AR(Eos) patients than in AR(Neu) patients (1.99 vs 1.50, P=0.02). Comparing AR(Eos) patients with AR(Neu1) patients 2 weeks after treatment, nasal symptoms and VAS were significantly lower in AR(Eos) patients, except for nasal blockage symptoms (P<0.05 of nasal itching and sneezing; P<0.01 for nasal secretion, total scores, and VAS). Comparing AR(Neu1) with AR(Neu2) patients, nasal symptoms, and VAS were significantly lower in AR(Neu2), except for nasal blockage and nasal itching symptoms (P<0.05 for nasal secretions, sneezing, total score, and VAS).ConclusionsNasal cytology may have important value in subtyping AR and optimizing AR treatment. Treating neutrophils is very important in AR patients with locally predominant neutrophils.
| S-EPMC5500694 | biostudies-literature
Project description:BackgroundPseudomonas aeruginosa causes chronic respiratory disease, and the elastase enzyme that it produces increases the permeability of airway epithelial cells owing to the disruption of tight junctions. P. aeruginosa is also implicated in prolonged chronic rhinosinusitis. However, the effects of P. aeruginosa elastase (PE) against the barrier formed by human nasal epithelial cells (HNECs) remain unknown.MethodsTo investigate the mechanisms involved in the disruption of tight junctions by PE in HNECs, primary cultures of HNECs transfected with human telomerase reverse transcriptase (hTERT-HNECs) were used. The hTERT-HNECs were pretreated with inhibitors of various signal transduction pathways, PKC, MAPK, p38MAPK, PI3K, JNK, NF-?B, EGF receptor, proteasome, COX1 and COX2 before treatment with PE. Some cells were pretreated with siRNA and agonist of protease activated receptor-2 (PAR-2) before treatment with PE. Expression and structures of tight junctions were determined by Western blotting, real-time PCR, immunostaining and freeze-fracture. Transepithelial electrical resistance (TER) was examined as the epithelial barrier function.ResultsPE treatment transiently disrupted the epithelial barrier and downregulated the transmembrane proteins claudin-1 and -4, occludin, and tricellulin, but not the scaffold PDZ-expression proteins ZO-1 and -2 and adherens junction proteins E-cadherin and ?-catenin. The transient downregulation of tight junction proteins was controlled via distinct signal transduction pathways such as the PKC, MAPK, PI3K, p38 MAPK, JNK, COX-1 and -2, and NF-?B pathways. Furthermore, treatment with PE transiently decreased PAR-2 expression, which also regulated the expression of the tight junction proteins. Treatment with a PAR-2 agonist prevented the downregulation of the tight junction proteins after PE treatment in HNECs.ConclusionsPE transiently disrupts tight junctions in HNECs and downregulates PAR-2. The transient disruption of tight junctions by PE might occur repeatedly during chronic rhinosinusitis.
| S-EPMC3936699 | biostudies-literature