Expression of Toll-like receptors in nasal epithelium in allergic rhinitis.
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ABSTRACT:
SUBMITTER: Renkonen J
PROVIDER: S-EPMC4744727 | biostudies-other | 2015 Aug
REPOSITORIES: biostudies-other
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Project description:Allergic rhinitis represents a global health issue affecting 10% to 25% of the population worldwide. Over the years, studies have found that allergic diseases, including allergic rhinitis, are associated with immunological responses to antigens driven by a Th2-mediated immune response. Because Toll-like receptors (TLRs) are involved in both innate and adaptive immune responses to a broad variety of antigens, the association between polymorphisms of TLRs and allergic diseases has been the focus in many animal and human studies. Although the etiology of allergic rhinitis is still unknown, extensive research over the years has confirmed that the underlying causes of allergic diseases are due to many genetic and environmental factors, along with the interactions among them, which include gene-environment, gene-gene, and environment-environment interactions. Currently, there is great inconsistency among studies mainly due to differences in genetic background and unique gene-environment interactions. This paper reviews studies focusing on the association between TLR polymorphisms and allergic diseases, including allergic rhinitis, which would help researchers better understand the role of TLR polymorphisms in the development of allergic rhinitis, and ultimately lead to more efficient therapeutic interventions being developed.
| S-EPMC3681168 | 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:BACKGROUND:Variation in the 10 toll-like receptor (TLR) genes has been significantly associated with allergic rhinitis (AR) in several candidate gene studies and three large genome-wide association studies. These have all investigated common variants, but no investigations for rare variants (MAF???1%) have been made in AR. The present study aims to describe the genetic variation of the promoter and coding sequences of the 10 TLR genes in 288 AR patients. METHODS:Sanger sequencing and Ion Torrent next-generation sequencing was used to identify polymorphisms in a Swedish AR population and these were subsequently compared and evaluated using 1000Genomes and Exome Aggregation Consortium (ExAC) data. RESULTS:The overall level of genetic variation was clearly different among the 10 TLR genes. The TLR10-TLR1-TLR6 locus was the most variable, while the TLR7-TLR8 locus was consistently showing a much lower level of variation. The AR patients had a total of 37 promoter polymorphisms with 14 rare (MAF???1%) and 14 AR-specific polymorphisms. These numbers were highly similar when comparing the AR and the European part of the 1000Genomes populations, with the exception of TLR10 where a significant (P?=?0.00009) accumulation of polymorphisms were identified. The coding sequences had a total of 119 polymorphisms, 68 were rare and 43 were not present in the European part of the 1000Genomes population. Comparing the numbers of rare and AR-specific SNPs in the patients with the European part of the 1000Genomes population it was seen that the numbers were quite similar both for individual genes and for the sum of all 10 genes. However, TLR1, TLR5, TLR7 and TLR9 showed a significant excess of rare variants in the AR population when compared to the non-Finnish European part of ExAC. In particular the TLR1 S324* nonsense mutation was clearly overrepresented in the AR population. CONCLUSIONS:Most TLR genes showed a similar level of variation between AR patients and public databases, but a significant excess of rare variants in AR patients were detected in TLR1, TLR5, TLR7, TLR9 and TLR10. This further emphasizes the frequently reproduced TLR10-TLR1-TLR6 locus as being involved in the pathogenesis of allergic rhinitis.
| S-EPMC5322632 | biostudies-literature
Project description:Nasal 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.Nasal 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.There 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).Nasal 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-other
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:BACKGROUND: The link between upper and lower airways in patients with both asthma and allergic rhinitis is still poorly understood. As the biological complexity of these disorders can be captured by gene expression profiling we hypothesized that the clinical expression of rhinitis and/or asthma is related to differential gene expression between upper and lower airways epithelium. OBJECTIVE: Defining gene expression profiles of primary nasal and bronchial epithelial cells from the same individuals and examining the impact of allergic rhinitis with and without concomitant allergic asthma on expression profiles. METHODS: This cross-sectional study included 18 subjects (6 allergic asthma and allergic rhinitis; 6 allergic rhinitis; 6 healthy controls). The estimated false discovery rate comparing 6 subjects per group was approximately 5%. RNA was extracted from isolated and cultured epithelial cells from bronchial brushings and nasal biopsies, and analyzed by microarray (Affymetrix U133+ PM Genechip Array). Data were analysed using R and Bioconductor Limma package. For gene ontology GeneSpring GX12 was used. RESULTS: The study was successfully completed by 17 subjects (6 allergic asthma and allergic rhinitis; 5 allergic rhinitis; 6 healthy controls). Using correction for multiple testing, 1988 genes were differentially expressed between healthy lower and upper airway epithelium, whereas in allergic rhinitis with or without asthma this was only 40 and 301 genes, respectively. Genes influenced by allergic rhinitis with or without asthma were linked to lung development, remodeling, regulation of peptidases and normal epithelial barrier functions. CONCLUSIONS: Differences in epithelial gene expression between the upper and lower airway epithelium, as observed in healthy subjects, largely disappear in patients with allergic rhinitis with or without asthma, whilst new differences emerge. The present data identify several pathways and genes that might be potential targets for future drug development.
| S-EPMC3839950 | biostudies-literature
Project description:BackgroundLong noncoding RNAs (lncRNAs) are involved in a variety of human immune diseases. However, the expression profile and precise function of lncRNAs in allergic rhinitis (AR) remain unknown. In the present study, genome-wide analysis of lncRNA expression was performed in the nasal mucosa tissue and mRNA regulatory relationship was examined among patients with or without AR.MethodsMicroarray assays were performed and the differential expressions of lncRNAs or mRNA were verified through RT-PCR. The lncRNA functions were annotated using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). The potential regulatory relationships between lncRNAs and the co-expressed mRNAs were analyzed using Cytoscape software. The expressions of specific lncRNAs and mRNAs were examined using an in vitro cell model.ResultsA total of 57 lncRNAs and 127 mRNAs were dysregulated in the nasal mucosa tissue of patients with AR, compared to those of patients without AR (fold change > 2.0 and P < 0.05). GO and pathway analysis indicated that the lncRNA-co-expressed mRNAs were enriched in several biological processes and cellular signaling pathways related to AR, such as positive regulation of the integrin biosynthetic process, cell adhesion, and leukocyte transendothelial migration. Some lncRNAs regulated the co-expressed genes in a cis- and/or trans-regulatory manner. Furthermore, allergen exposure significantly increased the expression of lnc-CXCL12-4, CXCL12, and CXCR4 in BEAS-2B cells compared to untreated cells (P < 0.01).ConclusionThe results of the present study suggest that lncRNAs participate in the biological pathways related to AR. Leukocyte transepithelial migration may be a potential target for lncRNAs to regulate allergic inflammation and CXCL12/CXCR4 axis plays an important role in the inflammatory process of AR.
| S-EPMC8033732 | biostudies-literature
Project description:BackgroundAllergic rhinitis is characterized by nasal inflammation in response to allergen exposure. Nasal allergen challenges are used in clinical trials evaluating drug effects. Reproducibility of nasal secretion cytokine responses and physiological measurements are needed to determine the optimum measurements and power calculations for future studies. We have investigated the reproducibility of nasal cytokine measurements, using ready-to-use polyvinyl acetate sponges to collect nasal secretions, and measurements of nasal physiological responses.MethodsTwelve subjects with allergic rhinitis and no history of respiratory disease, and 12 subjects with asthma and allergic rhinitis underwent a nasal allergen challenge. This was repeated at 7-14 days later.ResultsThere were increases in IL-5, CCL11, and CXCL8 responses post-challenge (all P<0.05). There was better reproducibility at later time points when higher cytokine levels were detected for IL-5 (ri =0.64 at 8 hours) and CXCL8 (ri =0.91 at 8 hours). Acoustic rhinometry provided good to excellent reproducibility (ri =0.66-0.89). Rhinomanometry had lower reproducibility with greater variation (ri =0.10-0.70), with some subjects unable to perform the measurement. Multiplex immunoassays provided greater sensitivity for CCL11 measurements. There were no differences between allergic rhinitis patients with and without asthma.ConclusionPolyvinyl acetate sponges are a practical and reproducible way to sample nasal secretions. Acoustic rhinometry is a practical and reproducible method for assessing physiological responses. There were no differences in nasal response due to the presence of concurrent asthma.
| S-EPMC6521845 | biostudies-literature
Project description:Analysis of nasal epithelial cells from adult patients with seasonal allergic rhinitis and from non allergic controls. Results provide insight into the molecular mechanisms associated with inflammatory responses in nasal mucosa. Total RNA was obtained from nasal epithelial cells of 7 seasonal allergic rhinitis patients and 5 non-allergic control subjects
2015-01-16 | E-GEOD-43523 | biostudies-arrayexpress
Project description:Analysis of nasal epithelial cells from adult patients with seasonal allergic rhinitis and from non allergic controls. Results provide insight into the molecular mechanisms associated with inflammatory responses in nasal mucosa.
2015-01-16 | GSE43523 | GEO