RESUMEN

OBJECTIVES: Previous studies have revealed a correlation between eosinophils and allergic rhinitis, but the causal relationship has not been fully confirmed. This study aims to evaluate the causal link between blood eosinophils and allergic rhinitis using the Mendelian randomization (MR) method. METHODS: Summary data from the Genome-Wide Association Study Catalog (GWAS) for eosinophil count (exposure variable) and allergic rhinitis (outcome variable) were collected. GWAS data for the exposure variable were obtained from the IEU Open GWAS Project developed by the Integrative Epidemiology Unit at the University of Bristol, while data for the outcome variable were sourced from the FinnGen Biobank (Finland) database. The causal relationship between eosinophils and allergic rhinitis was analyzed using the two-sample MR method with inverse variance weighted (IVW) analysis. Sensitivity analyses were conducted using the weighted median method, MR-Egger regression, leave-one-out analysis, and funnel plots. RESULTS: An increase in blood eosinophil count showed a potential causal relationship with an increased risk of allergic rhinitis (OR=1.187, 95% CI 1.051 to 1.341, P=0.006). This finding was consistent across the weighted median method and MR-Egger regression. Leave-one-out analysis indicated that no single nucleotide polymorphism significantly influenced the causal inference. CONCLUSIONS: There is a causal association between increased eosinophil count and a higher risk or worsening of allergic rhinitis.

Asunto(s)

Eosinófilos , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Polimorfismo de Nucleótido Simple , Rinitis Alérgica , Humanos , Rinitis Alérgica/genética , Rinitis Alérgica/etiología , Recuento de Leucocitos , Factores de Riesgo

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Several studies reveal that allergic rhinitis (AR) is a significant risk factor of systemic lupus erythematosus (SLE). However, studies investigating the common pathogenesis linking AR and SLE are lacking. Our study aims to search for the shared biomarkers and mechanisms that may provide new therapeutic targets for preventing AR from developing SLE. GSE50223 for AR and GSE103760 for SLE were downloaded from the Gene Expression Omnibus (GEO) database to screen differentially expressed genes (DEGs). The Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed to explore the functions of shared DEGs. Hub genes were screened by cytoHubba (a plugin of Cytoscape) and validated in another two datasets. Gene set enrichment analysis (GSEA) and single-sample Gene set enrichment analysis (ssGSEA) algorithm were applied to understand the functions of hub gene. ENTPD1 was validated as a hub gene between AR and SLE. GSEA results revealed that ENTPD1 was associated with KRAS_SIGNALING_UP pathway in AR and related to HYPOXIA, TGF_BETA_SIGNALING and TNFA_SIGNALING_VIA_NFKB pathways in SLE. The expression of ENTPD1 was positively correlated with activated CD8 T cell in both diseases. Thus, ENTPD1 may be a novel therapeutic target for preventing AR from developing SLE.

Asunto(s)

Biomarcadores , Lupus Eritematoso Sistémico , Rinitis Alérgica , Humanos , Lupus Eritematoso Sistémico/genética , Rinitis Alérgica/genética , Ontología de Genes , Perfilación de la Expresión Génica , Bases de Datos Genéticas , Transducción de Señal , Redes Reguladoras de Genes , Biología Computacional/métodos

RESUMEN

Objective: To explore the causal relationship between asthma, allergic rhinitis (AR), and chronic sinusitis (CRS), using two sample Mendelian randomization (MR) analysis, thereby providing foundational evidences for the pathogenesis and treatment of CRS. Methods: The genetic variations in AR and asthma were used as instrumental variables, with genetic data from the Integrated Epidemiology Unit (IEU) Open database. A total of 14 283 asthma and 18 934 AR cases were included, with 98 300 and 64 595 corresponding normal control cases, respectively. For CRS, there were 3 236 CRSwNP and 8 524 CRSsNP, respectively, with 167 849 and 167 849 corresponding normal control cases, respectively. The genetic data were analyzed using the inverse variance weighting method (IVW), MR Egger method, weighted median method, and Cochran's Q-test. Results: The IVW analysis showed that asthma increased the risk of both CRSwNP (OR=482.8, 95%CI: 57.18-4 077.78, P<0.001) and CRSsNP (OR=25.73, 95%CI: 9.79-67.56, P<0.001); AR significantly increased the risk of CRSsNP (OR=5.40, 95%CI: 1.68-17.26, P=0.004), but not CRSwNP (OR=7.38, 95%CI: 0.80-67.73, P=0.077). Conversely, neither CRSwNP nor CRSsNP increased the risk of asthma or AR. Conclusion: According to Mendelian genetic laws, asthma is a risk factor for CRSwNP and CRSsNP, while AR is a risk factor for CRSsNP.

Asunto(s)

Asma , Análisis de la Aleatorización Mendeliana , Rinitis Alérgica , Sinusitis , Humanos , Asma/genética , Asma/etiología , Asma/epidemiología , Sinusitis/genética , Sinusitis/etiología , Rinitis Alérgica/epidemiología , Rinitis Alérgica/genética , Enfermedad Crónica , Factores de Riesgo

RESUMEN

Objective: To determine the causal relationship between educational attainment and the risk of allergic rhinitis and (or) eczema using Mendelian randomization (MR) analyses. Methods: This study was a secondary data analysis based on the summary data of genome-wide association studies (GWAS), which involved 293 723 participants (educational attainment) from the Social Science Genetics Association Consortium and 462 013 participants [allergic rhinitis and (or) eczema] from the UK Biobank. Genetic variants that were closely related to educational attainment were identified as instrumental variables. Two-sample MR analyses, including inverse-variance weighted (IVW), MR-Egger regression, weighted median method and weighted model-based estimation, were performed to investigate the causal relationship between educational attainment and the risk of allergic rhinitis and (or) eczema, in which the odds ratio (OR) values were used as indicators. Results: A total of 70 single-nucleotide polymorphisms (SNPs) were chosen as instrumental variables. The MR-Egger regression results suggested that the genetic pleiotropy was unlikely to bias our results (P=0.107). In the univariable MR analyses, IVW regression showed that the risk of allergic rhinitis and (or) eczema was OR=1.044 (95%CI: 1.020-1.069, P<0.001) and OR=1.170 (95%CI: 1.074-1.256, P<0.001), respectively, for the increase in the duration of education by one year or one standard deviation (SD) (3.71 years). In the reverse MR analysis, IVW regression showed little evidence that allergic rhinitis and (or) eczema affected educational attainment (OR=1.020, 95%CI: 0.927-1.023, P=0.683). The results of the weighted median method and weighted mode-based estimation were consistent with the results of IVW. Conclusion: This study suggests that there is a positive causal relationship between educational attainment and the risk of allergic rhinitis and (or) eczema, which means that educational attainment can increase the occurrence of allergic rhinitis and (or) eczema.

Asunto(s)

Eccema , Escolaridad , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Polimorfismo de Nucleótido Simple , Rinitis Alérgica , Humanos , Rinitis Alérgica/genética , Rinitis Alérgica/epidemiología , Eccema/genética , Eccema/epidemiología , Factores de Riesgo , Predisposición Genética a la Enfermedad

RESUMEN

Background: Allergic rhinitis (AR) is a complex disease in which gene-environment interactions contribute to its pathogenesis. Epigenetic modifications, such as N6-methyladenosine (m6A) modification of mRNA, play important roles in regulating gene expression in multiple physiological and pathological processes. However, the function of m6A modification in AR and the inflammatory response is poorly understood. Methods: We used the ovalbumin (OVA) and aluminum hydroxide to induce an AR mouse model. Nasal symptoms, histopathology, and serum cytokines were examined. We performed combined m6A and RNA sequencing to analyze changes in m6A modification profiles. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and methylated RNA immunoprecipitation sequencing qPCR (MeRIP-qPCR) were used to verify differential methylation of mRNAs and the m6A methylation level. Knockdown or inhibition of Alkbh5 in nasal mucosa of mice was mediated by lentiviral infection or IOX1 treatment. Results: We showed that m6A was enriched in a group of genes involved in MAPK signaling pathway. Moreover, we identified a MAPK pathway involving Map3k8, Erk2, and Nfκb1 that may play a role in the disrupted inflammatory response associated with nasal inflammation. The m6A eraser, Alkbh5, was highly expressed in the nasal mucosa of AR model mice. Furthermore, knockdown of Alkbh5 expression by lentiviral infection resulted in high MAPK pathway activity and a significant nasal mucosa inflammatory response. Our findings indicate that ALKBH5-mediated m6A dysregulation likely contributes to a nasal inflammatory response via the MAPK pathway. Conclusion: Together, our data show that m6A dysregulation mediated by ALKBH5, is likely to contribute to inflammation of the nasal mucosa via the MAPK signaling pathway, suggesting that ALKBH5 is a potential biomarker for AR treatment.

Asunto(s)

Adenosina , Desmetilasa de ARN, Homólogo 5 de AlkB , Modelos Animales de Enfermedad , Sistema de Señalización de MAP Quinasas , Mucosa Nasal , ARN Mensajero , Rinitis Alérgica , Animales , Mucosa Nasal/inmunología , Mucosa Nasal/metabolismo , Mucosa Nasal/patología , Rinitis Alérgica/inmunología , Rinitis Alérgica/metabolismo , Rinitis Alérgica/genética , Ratones , Adenosina/análogos & derivados , Adenosina/metabolismo , Metilación , ARN Mensajero/genética , ARN Mensajero/metabolismo , Desmetilasa de ARN, Homólogo 5 de AlkB/metabolismo , Desmetilasa de ARN, Homólogo 5 de AlkB/genética , Femenino , Ratones Endogámicos BALB C , Inflamación/genética , Inflamación/inmunología , Citocinas/metabolismo

RESUMEN

Backgrounds: Observational studies suggest that air pollutants, including particulate matter and nitrogen compounds, could elevate asthma and allergic rhinitis health risks. Nevertheless, the exact nature of the causal relationship between air pollution and asthma and allergic rhinitis remains unknown. This study utilizes the Mendelian randomization (MR) technique to explore the potential causal links between air pollution components (PM2.5, PM2.5-10, PM10, NO2, and nitrogen dioxide) and the incidence of allergic rhinitis and asthma. Methods: A MR study utilized summary statistics from GWAS that are publicly accessible. The inverse variance weighting (IVW) approach served as the foundational analysis technique. To ensure robustness, supplementary methodologies such as the weighted median, MR-Egger regression, simple mode, and weighted model were also applied. Heterogeneity was evaluated using Cochran's Q test, and the presence of pleiotropy was determined through MR-Egger regression. The MR-PRESSO test was employed for outlier detection, and the analysis's sensitivity was scrutinized via a leave-one-out strategy. Results: The IVW technique showed a strong correlation between PM10 and asthma (OR = 0.625, 95% CI = 0.396-0.988, p = 0.044). No significant associations were found between asthma and other air pollutants such as PM2.5, PM2.5-10, NO2, or nitrogen dioxide. Similarly, allergic rhinitis showed no causal relationships with any studied air pollution metrics. Pleiotropy was absent in the findings. Sensitivity analyses, employing the leave-one-out method, confirmed the stability of these results, unaffected by individual single nucleotide polymorphisms (SNPs). Conclusion: This Mendelian randomization study establishes a causal link between PM10 exposure and asthma, suggesting that interventions to reduce air pollution may decelerate the adverse progression of asthma.

Asunto(s)

Contaminación del Aire , Asma , Análisis de la Aleatorización Mendeliana , Material Particulado , Rinitis Alérgica , Asma/genética , Asma/epidemiología , Asma/etiología , Humanos , Rinitis Alérgica/genética , Rinitis Alérgica/epidemiología , Rinitis Alérgica/etiología , Contaminación del Aire/efectos adversos , Material Particulado/efectos adversos , Contaminantes Atmosféricos/efectos adversos , Estudio de Asociación del Genoma Completo , Polimorfismo de Nucleótido Simple , Exposición a Riesgos Ambientales/efectos adversos , Causalidad

RESUMEN

BACKGROUND: A chronic condition that significantly reduces a child's quality of life is allergic rhinitis (AR). The environment and allergens that the body is regularly exposed to can cause inflammatory and immunological reactions, which can change the expression of certain genes Epigenetic changes are closely linked to the onset and severity of allergy disorders according to mounting amounts of data. Noncoding RNAs (ncRNAs) are a group of RNA molecules that cannot be converted into polypeptides. The three main categories of ncRNAs include microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs). NcRNAs play a crucial role in controlling gene expression and contribute to the development of numerous human diseases. METHODS: Articles are selected based on Pubmed's literature review and the author's personal knowledge. The largest and highest quality studies were included. The search selection is not standardized. RESULTS: Recent findings indicate that various categories of ncRNAs play distinct yet interconnected roles and actively contribute to intricate gene regulatory networks. CONCLUSION: This article demonstrates the significance and progress of ncRNAs in children's AR. The database covers three key areas: miRNAs, lncRNAs, and circRNAs. Additionally, potential avenues for future research to facilitate the practical application of ncRNAs as therapeutic targets and biomarkers will be explore.

Asunto(s)

ARN no Traducido , Rinitis Alérgica , Humanos , Rinitis Alérgica/genética , Rinitis Alérgica/inmunología , Niño , ARN no Traducido/genética , MicroARNs/genética , Biomarcadores/metabolismo

RESUMEN

BACKGROUND: Allergic rhinitis (AR) is an allergic disease characterized by the dominant differentiation of T helper cell 2 (Th2). BACH2 plays a key role in regulating Th2 immune response. This study aimed to explore the association between BACH2 single nucleotide polymorphism (SNPs) and susceptibility to AR. METHODS: Han population from northern Shaanxi, China was chosen as subjects. After the DNA extraction from the peripheral blood of subjects, genotyping was completed through the Agena MassARRAY platform. Logistic regression analysis was used to assess the association. Multivariate dimensionality reduction (MDR) was used to evaluate the effect of the interaction between 'SNP-SNP' on susceptibility to AR. Using false-positive report probability (FPRP) analysis to test whether the significant results obtained in this study were noteworthy. RESULTS: BACH2-rs905670 and -rs2134814 were significantly associated with increased risk of AR. The mutant allele 'A' of rs905670 (OR = 1.36, p = 0.018) and mutant allele 'G' of rs2134814 (OR = 1.34, p = 0.027) were risk genetic factors for AR. The above genetic association was further observed in the stratified analysis: BACH2-rs905670 and-rs2134814 were significantly associated with an increased risk of AR in females, aging older than 43 years, and participants working and living in the loess hills (OR > 1, p < 0.05). CONCLUSION: BACH2-rs905670 and -rs2134814 are significantly associated with increasing AR risk.

Asunto(s)

Factores de Transcripción con Cremalleras de Leucina de Carácter Básico , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Rinitis Alérgica , Células Th2 , Adolescente , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Alelos , Pueblo Asiatico/genética , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/genética , Estudios de Casos y Controles , China , Genotipo , Rinitis Alérgica/genética , Rinitis Alérgica/inmunología , Factores de Riesgo , Células Th2/inmunología

RESUMEN

Traditional studies on allergic rhinitis（AR） have mainly adopted animal models and biomolecular approaches. In addition, the advent of transcriptome sequencing technology is promoting the development of AR at the genetic level. Recently, many scholars have focused on the role of common RNA in the pathogenesis of AR, suggesting that breakthroughs have been made in the field of AR bioinformatics analysis. This review aims to summarize the research advances in AR, the development of transcriptome sequencing technology, and the application of transcriptome sequencing in AR, in order to explore potential drug targets for AR treatment and provide new insights into precision medicine.

Asunto(s)

Rinitis Alérgica , Transcriptoma , Rinitis Alérgica/genética , Humanos , Animales , Perfilación de la Expresión Génica/métodos , Biología Computacional/métodos , Análisis de Secuencia de ARN/métodos , Medicina de Precisión/métodos

RESUMEN

BACKGROUND: Chronic periodontitis (CP) and allergic rhinitis (AR) have attracted wide attention as global public health problems with high incidence. Recent studies have shown that circulating interleukin-27 (IL-27) is associated with the risk of CP and AR. The aim of this study is to analyze the causal effect between them using Mendelian randomization (MR). METHODS: Bidirectional MR analyses were performed with the use of publicly available genome-wide association study (GWAS) data. Summary data on circulating IL-27, CP, and AR published in genome-wide association studies were collected. Instrumental variables (IV) were extracted using assumptions of correlation, independence and exclusivity as criteria. Inverse variance weighting (IVW) was used as the main method, combined with weighted median method (WM) and MR-Egger and other MR Analysis methods for causal inference of exposure and outcome. Cochran's Q and MR-Egger intercept were used for sensitivity analysis. RESULTS: The IVW study showed a causal effect between increased circulating IL-27 levels and increased risk of CP (OR = 1.14, 95%CI = 1.02-1.26, p = .020). Similarly, the increase of circulating IL-27 level had a causal effect on the decreased risk of AR (OR = 0.88, 95%CI = 0.80-0.97, p = .012). In addition, IVW study found that there was a causal between the increased risk of CP and circulating IL-27 level (OR = 1.05, 95%CI = 1.01-1.10, p = .016). However, there was no significant causal relationship between the risk of AR and circulating IL-27 levels (OR = 0.97, 95%CI = 0.91-1.02, p = .209). no significant heterogeneity or horizontal pleiotropy was found in sensitivity analysis. CONCLUSIONS: There is a causal effect between circulating IL-27 level and CP, AR, which will help to find new ideas and methods for the diagnosis and treatment of CP and AR.

Asunto(s)

Periodontitis Crónica , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Polimorfismo de Nucleótido Simple , Rinitis Alérgica , Humanos , Rinitis Alérgica/genética , Rinitis Alérgica/sangre , Rinitis Alérgica/epidemiología , Rinitis Alérgica/inmunología , Periodontitis Crónica/genética , Periodontitis Crónica/sangre , Periodontitis Crónica/diagnóstico , Predisposición Genética a la Enfermedad , Interleucinas/genética , Interleucinas/sangre , Factores de Riesgo , Interleucina-27/sangre , Interleucina-27/genética

RESUMEN

Background: Allergic rhinitis (AR), a prevalent chronic inflammatory condition triggered by immunoglobulin E (IgE), involves pivotal roles of immune and metabolic factors in its onset and progression. However, the intricacies and uncertainties in clinical research render current investigations into their interplay somewhat inadequate. Objective: To elucidate the causal relationships between immune cells, metabolites, and AR, we conducted a mediation Mendelian randomization (MR) analysis. Methods: Leveraging comprehensive publicly accessible summary-level data from genome-wide association studies (GWAS), this study employed the two-sample MR research method to investigate causal relationships among 731 immune cell phenotypes, 1400 metabolite levels, and AR. Additionally, employing the mediation MR approach, the study analyzed potential mediated effect of metabolites in the relationships between immune cells and AR. Various sensitivity analysis methods were systematically employed to ensure the robustness of the results. Results: Following false discovery rate (FDR) correction, we identified three immune cell phenotypes as protective factors for AR: Naive CD8br %CD8br (odds ratio (OR): 0.978, 95% CI = 0.966-0.990, P = 4.5×10-4), CD3 on CD39+ activated Treg (OR: 0.947, 95% CI = 0.923-0.972, P = 3×10-5), HVEM on CD45RA- CD4+ (OR: 0.967, 95% CI = 0.948-0.986, P = 4×10-5). Additionally, three metabolite levels were identified as risk factors for AR: N-methylhydroxyproline levels (OR: 1.219, 95% CI = 1.104-1.346, P = 9×10-5), N-acetylneuraminate levels (OR: 1.133, 95% CI = 1.061-1.211, P = 1.7×10-4), 1-stearoyl-2-arachidonoyl-gpc (18:0/20:4) levels (OR: 1.058, 95% CI = 1.029-1.087, P = 5×10-5). Mediation MR analysis indicated a causal relationship between Naive CD8br %CD8br and N-methylhydroxyproline levels, acting as a protective factor (OR: 0.971, 95% CI = 0.950-0.992, P = 8.31×10-3). The mediated effect was -0.00574, accounting for 26.1% of the total effect, with a direct effect of -0.01626. Naive CD8+ T cells exert a protective effect on AR by reducing N-methylhydroxyproline levels. Conclusion: Our study, delving into genetic information, has substantiated the intricate connection between immune cell phenotypes and metabolite levels with AR. This reveals a potential pathway to prevent the onset of AR, providing guiding directions for future clinical investigations.

Asunto(s)

Linfocitos T CD8-positivos , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Polimorfismo de Nucleótido Simple , Rinitis Alérgica , Humanos , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Rinitis Alérgica/inmunología , Rinitis Alérgica/genética , Fenotipo , Predisposición Genética a la Enfermedad

RESUMEN

BACKGROUND: Allergic Rhinitis (AR) is a prevalent chronic non-infectious inflammation affecting the nasal mucosa. NLRP3-mediated pyroptosis of epithelial cells plays a pivotal role in AR pathogenesis. Herein, we evaluated the impact of the long non-coding RNA nuclear paraspeckle assembly transcript 1 (lncRNA NEAT1) on NLR family pyrin domain containing 3 (NLRP3)-mediated pyroptosis in AR. METHODS: Nasal inflammation levels in ovalbumin (OVA)-induced AR mice were assessed using HE staining, and NLRP3 expression was evaluated through immunohistochemistry. ELISA was utilized to detect OVA-specific IgE, IL-6, IL-5, and inflammatory cytokines (IL-1ß, IL-18). Human nasal epithelial cells (HNEpCs) stimulated with IL4/IL13 were used to analyze the mRNA and protein levels of associated genes utilizing RT-qPCR and western blot, respectively. Cell viability and pyroptosis were assessed by CCK-8 and flow cytometry. The targeting relationship between NEAT1, PTBP1 and FOXP1 were analyzed by RIP and RNA pull down assays. FISH and IF analysis were performed to assess the co-localization of NEAT1 and PTBP1. RESULTS: In both the AR mouse and cellular models, increased levels of NEAT1, PTBP1 and FOXP1 were observed. AR mice exhibited elevated inflammatory infiltration and pyroptosis, evidenced by enhanced expressions of OVA-specific IgE, IL-6, and IL-5, NLRP3, Cleaved-caspase 1, GSDMD-N, IL-1ß and IL-18. Functional assays revealed that knockdown of PTBP1 or NEAT1 inhibited pyroptosis while promoting the proliferation of IL4/IL13-treated HNEpCs. Mechanistically, NEAT1 directly interacted with PTBP1, thereby maintaining FOXP1 mRNA stability. Rescue assays demonstrated that FOXP1 upregulation reversed the inhibitory effects of silencing NEAT1 or PTBP1 on IL4/IL13-stimulated pyroptosis activation in HNEpCs. CONCLUSION: NEAT1 acts as a RNA scaffold for PTBP1, activating the PTBP1/FOXP1 signaling cascade, subsequently triggering NLRP3-mediated pyroptosis in HNEpCs, and ultimately promoting AR progression. These findings highlight some new insights into the pathogenesis of AR.

Asunto(s)

Factores de Transcripción Forkhead , Proteína con Dominio Pirina 3 de la Familia NLR , Mucosa Nasal , Piroptosis , ARN Largo no Codificante , Rinitis Alérgica , Animales , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/genética , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Rinitis Alérgica/inmunología , Rinitis Alérgica/patología , Rinitis Alérgica/genética , Rinitis Alérgica/metabolismo , Humanos , Ratones , Factores de Transcripción Forkhead/metabolismo , Factores de Transcripción Forkhead/genética , Mucosa Nasal/inmunología , Mucosa Nasal/patología , Mucosa Nasal/metabolismo , Ratones Endogámicos BALB C , Ovalbúmina/inmunología , Ribonucleoproteínas Nucleares Heterogéneas/metabolismo , Ribonucleoproteínas Nucleares Heterogéneas/genética , Transducción de Señal , Modelos Animales de Enfermedad , Femenino , Citocinas/metabolismo

RESUMEN

Allergic rhinitis is a prevalent inflammatory condition that impacts individuals of all age groups. Despite reports indicating the potential of berberine in alleviating allergic rhinitis symptoms, the specific molecular mechanisms and therapeutic targets of berberine remain unclear. This research aims to explore the pharmacological mechanism of berberine in the treatment of allergic rhinitis through bioinformatic analyses and experimental validation. The research utilized public databases to identify potential targets of berberine. Furthermore, differentially expressed genes (DEGs) related to allergic rhinitis were pinpointed from the GSE52804 dataset. Through bioinformatics techniques, the primary targets were discovered and key KEGG and GO-BP pathways were established. To confirm the therapeutic mechanisms of berberine on allergic rhinitis, an OVA-induced allergic rhinitis model was developed using guinea pigs. We identified 32 key genes responsible for the effectiveness of berberine in treating allergic rhinitis. In addition, five central genes (Alb, Il6, Tlr4, Ptas2, and Il1b) were pinpointed. Further examination using KEGG and GO-BP pathways revealed that the main targets were primarily involved in pathways such as NF-kappa B, IL-17, TNF, and inflammatory response. Molecular docking analysis demonstrated that berberine exhibited strong affinity towards these five key targets. Furthermore, the expression levels of IL-6, TLR4, PTGS2, and IL-1ß were significantly upregulated in the model group but downregulated following berberine treatment. This research has revealed the mechanism through which berberine combats allergic rhinitis and has identified its potential to regulate pathways linked to inflammation. These discoveries provide valuable insights for the development of novel medications for the treatment of allergic rhinitis.

Asunto(s)

Berberina , Biología Computacional , Simulación del Acoplamiento Molecular , Rinitis Alérgica , Berberina/farmacología , Berberina/uso terapéutico , Rinitis Alérgica/tratamiento farmacológico , Rinitis Alérgica/genética , Rinitis Alérgica/metabolismo , Animales , Cobayas , Biología Computacional/métodos , Modelos Animales de Enfermedad , Perfilación de la Expresión Génica , Humanos , Masculino , Ovalbúmina

RESUMEN

Allergic rhinitis is a common allergic disease with a complex pathogenesis and many unresolved issues. Studies have shown that the incidence of allergic rhinitis is closely related to genetic factors, and research on the related genes could help further understand its pathogenesis and develop new treatment methods. In this study, 446 allergic rhinitis-related genes were obtained on the basis of the DisGeNET database. The protein-protein interaction network was searched using the random-walk-with-restart algorithm with these 446 genes as seed nodes to assess the linkages between other genes and allergic rhinitis. Then, this result was further examined by three screening tests, including permutation, interaction, and enrichment tests, which aimed to pick up genes that have strong and special associations with allergic rhinitis. 52 novel genes were finally obtained. The functional enrichment test confirmed their relationships to the biological processes and pathways related to allergic rhinitis. Furthermore, some genes were extensively analyzed to uncover their special or latent associations to allergic rhinitis, including IRAK2 and MAPK, which are involved in the pathogenesis of allergic rhinitis and the inhibition of allergic inflammation via the p38-MAPK pathway, respectively. The new found genes may help the following investigations for understanding the underlying molecular mechanisms of allergic rhinitis and developing effective treatments.

Asunto(s)

Mapas de Interacción de Proteínas , Rinitis Alérgica , Humanos , Rinitis Alérgica/genética , Mapas de Interacción de Proteínas/genética , Bases de Datos Genéticas , Algoritmos , Biología Computacional/métodos , Redes Reguladoras de Genes

RESUMEN

Background: Airway allergic disease (AAD) is a class of autoimmune diseases with predominantly Th2-type inflammation, mainly including allergic rhinitis (AR), allergic asthma (AS), and chronic sinusitis (CRS). There are very complex regulatory mechanisms between immune cells and AAD; however, previous reports found that the functions of the same immune cells in AAD are not identical. Objective: The aim of this study was to explore the causal relationship between different phenotypic immune cells and their association with AAD. Method: Utilizing the publicly available Genome-Wide Association Studies (GWAS) database, this study conducted a bidirectional Mendelian randomization (MR) to assess the causal relationship between immune cells of 731 different immunophenotypes and AAD. The primary assessment methods included inverse variance weighting, weighted median, and MR Egger. Additionally, sensitivity analyses such as MR-PRESSO, leave-one-out, and scatter plots were employed to eliminate the interference of heterogeneity and pleiotropy, ensuring the stability of the causal inference. Result: A total of 38 immune cells with different immunophenotypes were found to be positively and causally associated with AR, of which 26 were protective factors and 12 were risk factors. Positive associations were found between 33 immune cells and AS, of which 14 were protective factors and 19 were risk factors, as well as between 39 immune cells and CRS, of which 22 were protective factors and 17 were risk factors. Finally, the results of all relevant immune cells for the three diseases were taken and intersected, and it was found that CD3 on CD39+-activated Treg (IVWAR = 0.001, IVWCRS = 0.043, IVWAS = 0.027) may be the key immune cell that inhibits the development of AAD (ORAR = 0.940, ORAS = 0.967, ORCRS = 0.976). Conclusion: This study reveals that different immune phenotypes of immune cells are closely related to AAD at the genetic level, which provides a theoretical basis for future clinical studies.

Asunto(s)

Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Fenotipo , Humanos , Asma/inmunología , Asma/genética , Inmunofenotipificación , Rinitis Alérgica/inmunología , Rinitis Alérgica/genética , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido Simple , Factores de Riesgo

RESUMEN

Background An increasing body of observational studies has indicated a potential link between allergic diseases, namely atopic dermatitis (AD), allergic rhinitis (AR), allergic asthma (AA), and psoriasis (PSO) as well as psoriatic arthritis (PSA). However, the presence and causal direction of this association remain uncertain. Methods We conducted two-sample Mendelian randomization (TSMR) analyses utilizing summary statistics derived from genome-wide association studies (GWAS) consortia. The summary statistics were obtained from a substantial participant cohort, consisting of 116,000 individuals (21,000 AD cases and 95,000 controls), 462,933 individuals (26,107 AR cases and 436,826 controls), and 140,308 individuals (4859 AA cases and 135,449 controls). The summary statistics for PSO (9267 cases and 360,471 controls) and PSA (3186 cases and 240,862 controls) were sourced from the FinnGen database. The primary analytical approach employed inverse variance weighting (IVW) as the main method within TSMR. We validated our findings through a series of sensitivity analyses. Furthermore, we performed reverse TSMR analyses to evaluate the potential presence of reverse causality. Results Our investigation revealed a potential protective effect of AD against both PSO (OR = 0.922, 95% CI = 0.863-0.984, p = 0.015)and PSA(OR = 0.915, 95% CI = 0.843-0.993, p = 0.033). Moreover, employing inverse MR analysis, we obtained compelling evidence supporting the protective role of PSO in preventing AD (OR = 0.891, 95% CI = 0.829-0.958, p = 0.002), as well as AR (OR = 0.998, 95% CI = 0.996-0.999, p = 0.008), these associations remained statistically significant even after Bonferroni correction was applied to account for multiple comparisons. Furthermore, our findings did not reveal any substantial causal relationship between AA and either PSO or PSA. Conclusion Our study provides compelling evidence that PSO significantly confers protection against both AD and AR, while AD is likely to act as a protective factor for both PSO and PSA. Despite previous studies suggesting an association between allergic diseases and the incidence of PSO and PSA, our findings do not support this claim. To obtain more accurate and reliable conclusions regarding the causal mechanisms involved, larger sample sizes in randomized controlled trials or MR studies are warranted.

Asunto(s)

Artritis Psoriásica , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Psoriasis , Humanos , Análisis de la Aleatorización Mendeliana/métodos , Artritis Psoriásica/genética , Artritis Psoriásica/epidemiología , Artritis Psoriásica/diagnóstico , Psoriasis/genética , Psoriasis/epidemiología , Psoriasis/inmunología , Polimorfismo de Nucleótido Simple , Rinitis Alérgica/genética , Rinitis Alérgica/epidemiología , Asma/genética , Asma/epidemiología , Dermatitis Atópica/genética , Dermatitis Atópica/epidemiología , Predisposición Genética a la Enfermedad

RESUMEN

OBJECTIVES: To observe effects of acupuncture at "Die E acupoint" on the protein expression levels of Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), nuclear transcription factor κB (NF-κB), transcription factor T-bet (T-bet), and GATA-binding protein-3 (GATA-3) in the nasal mucosa and the serum contents of related inflammatory cytokines in rats with allergic rhinitis, so as to explore the mechanism of acupuncture in treating allergic rhinitis. METHODS: Twenty-four healthy SD rats were randomly divided into blank, model, acupuncture, and sham acupuncture groups, with 6 rats in each group. The rat model of allergic rhinitis was established by using ovalbumin induction. The rats in the acupuncture group received bilateral acupuncture at the "Die E acupoint" with a depth of 15-20 mm, while the rats in the sham acupuncture group received only sham acupuncture (light and shallow acupunture of the skin at the "Die E acupoint" ). Both interventions were performed once daily for a total of 6 days. Behavioral scores of rats in each group were recorded. Pathological changes of nasal mucosa were observed by H.E. staining. Serum contents of IgE, ovalbumin-specific IgE (OVA-sIgE), interferon(IFN)-γ, interleukin(IL)-4, IL-10 and IL-17 were measured by ELISA and the protein expression levels of T-bet, GATA-3, TLR4, MyD88 and NF-κB p65 in the nasal mucosa were detected by Western blot. RESULTS: After modeling, compared with the blank group, rats in the model group showed increased behavioral scores, serum IgE, OVA-sIgE, IL-4, and IL-17 contents, and nasal mucosal GATA-3, TLR4, MyD88, and NF-κB p65 protein expression levels (P<0.05), whereas the contents of serum IFN-γ, IL-10 and the protein expression level of T-bet in the nasal mucosa were decreased (P<0.05). Comparison between the EA and model groups showed that acupuncture intervention can decrease the behavioral scores of rats with allergic rhinitis, the contents of serum IgE, OVA-sIgE, IL-4, IL-17, and the protein expression levels of GATA-3, TLR4, MyD88, and NF-κB p65 in the nasal mucosa (P<0.05), and up-regulate the contents of serum IFN-γ, IL-10, and the nasal mucosal T-bet protein expression level. Sham acupuncture did not have a significant modulating effect on the above indicators. Inflammatory infiltration of nasal mucosa was seen in the model group and sham acupuncture, and the inflammatory reaction was milder in the acupuncture group. CONCLUSIONS: Acupuncture at "Die E acupoint" can alleviate the symptoms of allergic rhinitis and suppress the inflammation of nasal mucosa in rats, which may be related to inhibiting the TLR4/MyD88/NF-κB signaling and balancing the levels of cytokines of Th1/Th2 and Treg/Th17, and T-bet/GATA-3.

Asunto(s)

Puntos de Acupuntura , Terapia por Acupuntura , Factor 88 de Diferenciación Mieloide , FN-kappa B , Rinitis Alérgica , Receptor Toll-Like 4 , Animales , Femenino , Humanos , Masculino , Ratas , Factor de Transcripción GATA3/metabolismo , Factor de Transcripción GATA3/genética , Factor de Transcripción GATA3/inmunología , Inmunoglobulina E/sangre , Inmunoglobulina E/inmunología , Interleucina-4/genética , Interleucina-4/inmunología , Interleucina-4/metabolismo , Factor 88 de Diferenciación Mieloide/metabolismo , Factor 88 de Diferenciación Mieloide/genética , Factor 88 de Diferenciación Mieloide/inmunología , FN-kappa B/metabolismo , FN-kappa B/genética , FN-kappa B/inmunología , Ratas Sprague-Dawley , Rinitis Alérgica/terapia , Rinitis Alérgica/inmunología , Rinitis Alérgica/metabolismo , Rinitis Alérgica/genética , Transducción de Señal , Receptor Toll-Like 4/metabolismo , Receptor Toll-Like 4/genética , Receptor Toll-Like 4/inmunología

RESUMEN

Objective To investigate the effect of lysine 27 residue of histone H3 (H3K27) acetylation modification on the transcriptional promotion of long noncoding RNA OPA interacting protein 5-antisense RNA 1 (lncRNA OIP5-AS1) and apoptosis of nasal epithelial cells (NECs) in allergic rhinitis (AR) via regulating Toll-like receptor 4 (TLR4). Methods Interleukin-13 (IL-13) was used to treat NECs to establish an AR cell model. Real-time quantitative PCR was utilized to detect the expressions of OIP5-AS1 and TLR4 in nasal mucosal tissues of AR patients and in the in vitro cell model. The concentrations of macrophage colony-stimulating factor (GM-CSF), eotaxin-1, and mucin 5AC (MUC5AC) were detected by ELISA. The apoptosis of NECs was determined by terminal deoxynucleotidyl transferase mediated dUTP-biotin nick end labeling (TUNEL). A dual-luciferase report experiment was carried out to verify the relationship between OIP5-AS1 and TLR4. Chromatin immunoprecipitation (ChIP) assay was performed to verify H3K27 acetylation of histones in the OIP5-AS1 promoter region. Results Compared with healthy controls and untreated NECs, OIP5-AS1 and TLR4 were both up-regulated in nasal mucosal tissues from AR patients and IL-13-stimulated NECs. Knockdown of OIP5-AS1 decreased the level of TLR4 in IL-13-treated NECs, while overexpression of OIP5-AS1 increased the level of TLR4. Inhibition of OIP5-AS1 reduced the apoptosis rate, and inhibited the secretion of GM-CSF, eotaxin-1, and MUC5AC from IL-13-treated NECs, while overexpression of TLR4 partially reversed the effects of OIP5-AS1 knockdown on NEC apoptosis and the secretion of GM-CSF, eotaxin-1, and MUC5AC. In addition, H3K27 acetylation was markedly enriched in the promoter region of OIP5-AS1, and H3K27 acetylation promoted the expression of OIP5-AS1 in IL-13-treated NECs. Conclusion H3K27 acetylation promotes OIP5-AS1 transcription and induces NEC apoptosis in AR via upregulation of TLR4.

Asunto(s)

Apoptosis , Células Epiteliales , Factor Estimulante de Colonias de Granulocitos y Macrófagos , Histonas , Mucosa Nasal , ARN Largo no Codificante , Rinitis Alérgica , Receptor Toll-Like 4 , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Acetilación , Quimiocina CCL11/genética , Quimiocina CCL11/metabolismo , Células Epiteliales/metabolismo , Factor Estimulante de Colonias de Granulocitos y Macrófagos/genética , Factor Estimulante de Colonias de Granulocitos y Macrófagos/metabolismo , Histonas/metabolismo , Histonas/genética , Interleucina-13/genética , Interleucina-13/metabolismo , Mucina 5AC/genética , Mucina 5AC/metabolismo , Mucosa Nasal/metabolismo , Rinitis Alérgica/genética , Rinitis Alérgica/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Receptor Toll-Like 4/genética , Receptor Toll-Like 4/metabolismo , Regulación hacia Arriba

Asunto(s)

Rinitis Alérgica , Humanos , Rinitis Alérgica/genética

RESUMEN

INTRODUCTION: Combined allergic rhinitis and asthma syndrome (CARAS) is a concurrent allergic symptom of diseases of allergic rhinitis and asthma. However, the mechanism of CARAS remains unclear. The study aimed to investigate the impact of microRNA-21 (miR-21) on CARAS via targeting poly (ADP-ribose) polymerase-1 (PARP-1) and phosphoinositide 3-kinase (PI3K)/AKT pathways. METHODS: The levels of miR-21-5p and PARP-1 in CARAS patients were detected by quantitative reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay (ELISA). An ovalbumin-sensitized mouse model of CARAS was established. And knock down of miR-21-5p was constructed by intranasally administering with miR-21-5p shRNA-encoding adeno-associated virus vector. Airway resistance and airway inflammatory response were detected. ELISA was used to evaluate IL-4/IL-5/IL-13 levels in bronchoalveolar lavage fluid (BALF). Expression levels of E-cadherin, fibronectin, and α-SMA were determined using Western blotting. The levels of PARP-1 and the activation of PI3K/AKT were assayed. RESULTS: Downregulation of miR-21-5p relieved pathophysiological symptoms of asthma including airway hyperreactivity and inflammatory cell infiltration. Downregulation of miR-21-5p significantly reduced the levels of IL4, IL-5, and IL-13 in BALF. Additionally, downregulation of miR-21-5p inhibited the epithelial-mesenchymal transition (EMT) process in CARAS mice. Furthermore, miR-21-5p regulated PARP-1 and was involved in PI3K/AKT activation in CARAS mice. CONCLUSION: Downregulation of miR-21-5p ameliorated CARAS-associated lung injury by alleviating airway inflammation, inhibiting the EMT process, and regulating PARP-1/PI3K/AKT in a mouse model of CARAS.

Asunto(s)

Asma , Modelos Animales de Enfermedad , Transición Epitelial-Mesenquimal , MicroARNs , Poli(ADP-Ribosa) Polimerasa-1 , Proteínas Proto-Oncogénicas c-akt , Rinitis Alérgica , Animales , MicroARNs/genética , Asma/metabolismo , Asma/genética , Asma/inmunología , Transición Epitelial-Mesenquimal/genética , Ratones , Rinitis Alérgica/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Poli(ADP-Ribosa) Polimerasa-1/metabolismo , Poli(ADP-Ribosa) Polimerasa-1/genética , Humanos , Fosfatidilinositol 3-Quinasas/metabolismo , Transducción de Señal , Femenino , Citocinas/metabolismo , Ratones Endogámicos BALB C , Ovalbúmina/inmunología , Masculino