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1.
Life Sci ; 241: 117101, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31778687

RESUMO

AIMS: Ten-eleven-translocation (Tet) proteins are 5-methylcytosine oxidases and have profound impact on DNA methylation and genes expression. This study aimed to investigate the role of Tet2 and its association with Foxp3 DNA methylation in regulatory T (Treg) cell of allergic rhinitis (AR). MATERIALS AND METHODS: CD4+CD25+Treg cells were sorted from peripheral blood lymphocytes drawn from AR patients and spleen lymphocytes drawn from OVA-exposed mice by flow cytometry. Tet2 and Foxp3 expressions were studied in sorted Treg cells. DNA methylation of CpG sites in Foxp3 in Treg cells was analyzed by pyrosequencing. TET2 protein binding to Foxp3 DNA in Treg cells was detected by chromatin immunoprecipitation followed by quantitative PCR (ChIP-qPCR). KEY FINDINGS: Treg cells drawn from AR patients and OVA-exposed mice showed reduction in cells counts, expression of Foxp3 mRNA and protein and down-regulation of Tet2, compared with the controls. Hypermethylation of Foxp3 TSDR and decline of TET2 binding to Foxp3 TSDR, but not promoter, were noted in Treg cells of OVA-exposed mice. Significant negative correlations between Tet2 expression and Foxp3 TSDR methylation, Foxp3 TSDR methylation and Foxp3 expression, and positive correlation between Foxp3 expression and Treg cells percentage were demonstrated by correlation analysis. SIGNIFICANCE: This study demonstrated that down-regulation of Tet2 was associated with higher methylation level of Foxp3 TSDR, reduction in Foxp3 expression and Treg cells percentage in AR, suggesting that Tet2 probably modulated the function of Treg cells in AR through Foxp3 methylation.


Assuntos
Metilação de DNA , Proteínas de Ligação a DNA/genética , Fatores de Transcrição Forkhead/genética , Proteínas Proto-Oncogênicas/genética , Rinite Alérgica/sangue , Linfócitos T Reguladores/patologia , Adolescente , Adulto , Idoso , Animais , Estudos de Casos e Controles , Proteínas de Ligação a DNA/metabolismo , Modelos Animais de Doenças , Regulação para Baixo , Feminino , Fatores de Transcrição Forkhead/metabolismo , Regulação da Expressão Gênica , Humanos , Imunoglobulina E/sangue , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Mucosa Nasal/patologia , Ovalbumina/toxicidade , Proteínas Proto-Oncogênicas/metabolismo , Rinite Alérgica/genética , Rinite Alérgica/imunologia , Linfócitos T Reguladores/metabolismo
2.
Int Arch Allergy Immunol ; 180(4): 235-243, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31694044

RESUMO

Over the last decades, an increasing appearance of allergies and atopic disorders, such as asthma, dermatitis, and rhinitis, has been observed. The mechanisms of these disorders remain unclear, and therefore the development of novel therapies is limited. Current treatments are often symptomatic, nonspecific, or may have severe side effects. Further insights into the mechanisms of the underlying disease pathogenesis could reveal novel targets for treatment. In this review, we provide an update on recent basic and translational studies that offer novel insights and opportunities for the treatment of patients with atopic disorders.


Assuntos
Asma/etiologia , Dermatite Atópica/etiologia , Hipersensibilidade Alimentar/etiologia , Rinite Alérgica/etiologia , Alérgenos/imunologia , Asma/genética , Asma/terapia , Dermatite Atópica/genética , Dermatite Atópica/terapia , Hipersensibilidade Alimentar/genética , Hipersensibilidade Alimentar/terapia , Predisposição Genética para Doença/genética , Humanos , Rinite Alérgica/genética , Rinite Alérgica/terapia , Fatores de Risco
3.
Hum Cell ; 32(4): 411-417, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31493245

RESUMO

Regulatory T cells (Tregs) play a crucial role in allergic rhinitis (AR). However, the mechanism of how Tregs are regulated in AR is poorly understood. Here, we aimed to explore the role of Tregs in AR and how Tregs were regulated by miR-202-5P, which was demonstrated to be important in AR. Peripheral blood mononuclear cells (PBMC) were isolated from collected blood samples. Tregs were purified using Regulatory T Cell Isolation Kit, and differentiated from isolated CD4 T cells using recombinant human interleukin-2 (rhIL-2) and transforming growth factor beta (TGF-ß). mRNA expression levels of miR-202-5p, matrilin-2 (MATN2), TGF-ß1 and interleukin-10 (IL-10) were detected by real-time PCR. The concentrations of IL-4, interleukin-17 (IL-17), IL-10, interferon gamma (IFN-γ) and TGF-ß1 were detected by enzyme-linked immunosorbent assay (ELISA). MATN2 protein level was detected by Western blot. MiR-202-5p expression dramatically elevated in PBMCs, CD4+ T cells and Tregs of AR patients. In vitro, miR-202-5p promoted Tregs differentiation via targeting MATN2. MiR-202-5p/MATN2 axis mediated Tregs proliferation and functions. MiR-202-5p/MATN2 are associated with regulatory T-cells differentiation and function in allergic rhinitis.


Assuntos
Diferenciação Celular/genética , MicroRNAs/genética , MicroRNAs/fisiologia , Rinite Alérgica/genética , Rinite Alérgica/imunologia , Linfócitos T Reguladores/fisiologia , Adulto , Feminino , Expressão Gênica , Humanos , Masculino , Proteínas Matrilinas/genética , Proteínas Matrilinas/metabolismo , Proteínas Matrilinas/fisiologia , Pessoa de Meia-Idade , Terapia de Alvo Molecular , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Rinite Alérgica/tratamento farmacológico , Linfócitos T Reguladores/imunologia , Adulto Jovem
4.
Int J Mol Sci ; 20(17)2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31470652

RESUMO

Atopic dermatitis (AD) is the most common inflammatory skin disease worldwide. It is a chronic, relapsing and pruritic skin disorder which results from epidermal barrier abnormalities and immune dysregulation, both modulated by environmental factors. AD is strongly associated with asthma and allergic rhinitis in the so-called 'atopic march.' Xenobiotic receptors and their mates are ligand-activated transcription factors expressed in the skin where they control cellular detoxification pathways. Moreover, they regulate the expression of genes in pathways involved in AD in epithelial cells and immune cells. Activation or overexpression of xenobiotic receptors in the skin can be deleterious or beneficial, depending on context, ligand and activation duration. Moreover, their impact on skin might be amplified by crosstalk among xenobiotic receptors and their mates. Because they are activated by a broad range of endogenous molecules, drugs and pollutants owing to their promiscuous ligand affinity, they have recently crystalized the attention of researchers, including in dermatology and especially in the AD field. This review examines the putative roles of these receptors in AD by critically evaluating the conditions under which the proteins and their ligands have been studied. This information should provide new insights into AD pathogenesis and ways to develop new therapeutic interventions.


Assuntos
Dermatite Atópica/metabolismo , Receptores Citoplasmáticos e Nucleares/metabolismo , Pele/metabolismo , Xenobióticos/metabolismo , Asma/genética , Asma/imunologia , Asma/metabolismo , Dermatite Atópica/genética , Dermatite Atópica/imunologia , Eczema/genética , Eczema/imunologia , Eczema/metabolismo , Epiderme/imunologia , Epiderme/metabolismo , Epiderme/patologia , Regulação da Expressão Gênica/imunologia , Ligantes , Receptores Citoplasmáticos e Nucleares/genética , Rinite Alérgica/genética , Rinite Alérgica/imunologia , Rinite Alérgica/metabolismo , Pele/imunologia , Pele/patologia
5.
Mol Med Rep ; 20(4): 3893-3900, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31485639

RESUMO

The aim of the present study was to investigate the expression and role of the co­stimulatory molecule T­lymphocyte activation antigen CD86 (CD86) in dendritic cells (DCs) from the peripheral blood of patients with allergic rhinitis (AR) compared with those from healthy individuals. It was observed that mature DCs from the peripheral blood of patients with AR expressed high levels of the co­stimulatory molecule CD86, but not CD80, compared with healthy control subjects. CD86 expression levels in DCs decreased significantly following transfection with siRNA in a lentiviral vector. Furthermore, the level of transforming growth factor­ß1 produced by T cells co­cultured with DCs was significantly increased in the siRNA group, while interleukin (IL)­4 and IL­5 production was significantly decreased. The findings of the present study indicated that CD86 may play a pivotal role in the regulatory T cell/type 2 helper T cell imbalance in allergic inflammation.


Assuntos
Antígenos CD/genética , Antígenos de Diferenciação Mielomonocítica/genética , Citocinas/genética , Células Dendríticas/metabolismo , Rinite Alérgica/genética , Linfócitos T/metabolismo , Células Cultivadas , Técnicas de Cocultura , Regulação para Baixo , Humanos , Interferência de RNA , RNA Interferente Pequeno/genética , Regulação para Cima
6.
Biomed Pharmacother ; 118: 109214, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31382129

RESUMO

OBJECTIVE: To investigate the effects of desmoglein 3 (DSG3) gene mediating epidermal growth factor/epidermal growth factor receptor (EGF/EGFR) signaling pathway on inflammatory response and immune function of anaphylactic rhinitis (AR). METHODS: Ten of the seventy male BALB/c mice were randomly selected as the normal control group, and the remaining 60 were used to construct the AR mice model. AR model mice were divided into 6 groups: model group (instilled with 5 µL saline), empty vector group (instilled with 5 µL of liposome and empty vector mixture), siRNA-DSG3 group (instilled with 5 µL of liposome and siRNA-DSG3 carrier mixture), AG1478 group (instilled with 5 µL of EGF/EGFR inhibitor AG1478), siRNA-DSG3+AG1478 group (instilled with 5 µL of liposome and siRNA-DSG3 carrier and EGF/EGFR inhibitor AG1478 mixture) and oe-DSG3 group, 10 in each group. After taking serum, each group of mice was sacrificed to get nasal mucosa tissues. HE staining was used to observe the pathological changes of nasal mucosa tissues in each group. The expression levels of DSG3, EGF and EGFR in nasal mucosa tissues of mice in each group were detected by qRT-PCR and western blot methods respectively. TUNEL staining was used to observe the apoptosis of nasal mucosa cells in mice. The expression of IgE, INF-γ, TNF-α, IL-2, IL-4 and IL-6 in serum of mice was determined by ELISA method. The immune adhesion function of red blood cells was detected by complement sensitization yeast hemagglutination method. RESULTS: All the mice with AR showed different degrees of nasal mucosa injury and inflammatory cell infiltration, and silencing DSG3 or inhibiting the activity of EGF signaling pathway could alleviate the nasal mucosa injury. Compared with control group, the INF-γ and IL-2 levels of serum in AR model mice were significantly decreased; IgE, TNF-α, IL-4 and IL-6 levels were significantly increased (all P < 0.05); the mRNA expression levels and protein levels of DSG3, EGF and EGFR were significantly increased (all P < 0.05); C3b receptor rosette rate and Ic rosette rate were significantly decreased (all P < 0.05). Detected by ELISA method, the expression levels of IgE, TNF-α, IL-4 and IL-6 were increased, while the expression levels of INF-γ and IL-2 were decreased after DSG3 silencing or using AG1478. Detected by qRT-PCR and western blot methods, the expression of DSG3, EGF and EGFR did decrease after DSG3 silencing. There was no significant difference in the EGF and EGFR expression between DSG3 silencing and using AG1478, and the expression decreased even more under the double effect. The mRNA and protein expression levels of DSG3, EGF and EGFR in the nasal mucosa tissues of mice with overexpression of DSG3 plasmid were significantly higher than those of normal mice (all P < 0.05). CONCLUSION: Silencing DSG3 gene can inhibit the activation of EGF signaling pathway, alleviate the inflammation of AR nasal mucosa, and enhance red blood cells immune adherence function.


Assuntos
Anafilaxia/imunologia , Desmogleína 3/genética , Fator de Crescimento Epidérmico/metabolismo , Receptores ErbB/metabolismo , Rinite Alérgica/imunologia , Anafilaxia/genética , Anafilaxia/metabolismo , Animais , Modelos Animais de Doenças , Fator de Crescimento Epidérmico/genética , Receptores ErbB/genética , Regulação da Expressão Gênica , Inflamação , Camundongos Endogâmicos BALB C , Mucosa Nasal/imunologia , Mucosa Nasal/metabolismo , Rinite Alérgica/genética , Rinite Alérgica/metabolismo , Transdução de Sinais
7.
Artigo em Chinês | MEDLINE | ID: mdl-31163545

RESUMO

Objective: To investigate the relationship between single nucleotide polymorphism(SNP) of vitamin D receptor(VDR) gene with susceptibility to allergic rhinitis(AR). Method: Two hundred and ten AR patients were selected as AR group, and 180 healthy volunteers from the same period were selected as control group. Fasting venous blood was collected from all subjects and blood DNA was extracted. Polymorphisms at ApaⅠ(rs7975232) and FokⅠ(rs2228570) loci of VDR gene were detected by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP), and the relationships between different genotypes with susceptibility to AR were comparatively analyzed. The Hardy-Weinberg's law of genetic balance verifies whether the two genotype frequencies were representative; Logistic multiple regression analysis was used to analyze the related factors affecting susceptibility of AR. Result: There were SNPs at rs7975232 locus of VDR gene, which were wild homozygote CC type, mutant heterozygote AC, and mutant homozygote AA. SNPs existed at rs2228570 locus, which were wild homozygote GG, mutant heterozygote GA, and mutant homozygote AA. The distributions of genotypes at rs7975232 and rs2228570 locus of VDR gene conformed to Hardy-Weinberg law. There was a significant difference in the distribution of rs7975232 genotype(P<0.05), and the frequency of C allele in the study group was significantly higher than that in the control group(P<0.05). There was no significant difference in genotype distribution of rs2228570 locus (P>0.05). Logistic analysis showed that CC genotype of ApaⅠwas a risk factor for AR susceptibility. Conclusion: The polymorphism of ApaⅠ(rs7975232) locus of VDR gene is correlated with AR susceptibility. CC genotype may be a susceptible factor for AR patients, but there is no significant correlation between FokⅠ polymorphism and AR. .


Assuntos
Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Receptores de Calcitriol/genética , Rinite Alérgica/genética , Estudos de Casos e Controles , Frequência do Gene , Genótipo , Humanos
8.
Hum Cell ; 32(3): 306-315, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31104300

RESUMO

Allergic rhinitis (AR) is a common hypersensitive disease that troubles patients a lot. Nasal epithelial cells (NECs), as the outmost protection of inhalation, play an important role in AR allergic response. Adrenoceptor beta 2 (ADRB2) is an important gene in inflammatory response, which has become the hot spot for AR development and treatment in recent years. MiR-15a-5p has been proved to be involved in AR immune response as the upstream regulator of ADRB2. Human primary NECs were isolated and stimulated by IL-13. qRT-PCR assay was used to detect the RNA level of target genes. ELISA and Western blotting were applied to detect target protein levels. Luciferase reporter assay and biotin pull-down assay were performed to test molecules interaction. ADRB2 was highly expressed in nasal mucosa of AR patients and was positively correlated with IL-13 stimulation, and knockdown of ADRB2 inhibited IL-13-induced expression of GM-CSF, eotaxin, and MUC5AC in NECs. ADRB2 was directly targeted by miR-15a-5p, and miR-15a-5p inhibited IL-13-induced expression of GM-CSF, eotaxin, and MUC5AC in NECs. ADRB2 mediated the effect of miR-15a-5p on the regulation of nasal epithelial immune responses. ADRB2 is negatively regulated by miR-15a-5p, which inhibits IL-13-induced nasal epithelial inflammatory responses.


Assuntos
Células Epiteliais/imunologia , Interleucina-13/imunologia , MicroRNAs/imunologia , Mucosa Nasal/citologia , Receptores Adrenérgicos beta 2/fisiologia , Rinite Alérgica/genética , Rinite Alérgica/imunologia , Células Cultivadas , Expressão Gênica , Regulação da Expressão Gênica , Humanos , Receptores Adrenérgicos beta 2/genética , Receptores Adrenérgicos beta 2/metabolismo
9.
Skin Pharmacol Physiol ; 32(4): 192-200, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31096247

RESUMO

BACKGROUND: Atopic diseases constitute a major health challenge for industrialized countries, and elevated levels of interleukin 4 (IL-4) frequently characterize these disorders. Previous in vitroanalyses have indicated that IL-4 strongly upregulates the expression of IL-4-sensitive genes in human monocytes. OBJECTIVE: To explore whether similar expression alterations may contribute to the pathomechanisms of atopic diseases in vivo we carried out a small-scale case-control clinical study (n = 43), in which we quantified the plasma levels of IgE and IL-4 as well as the expression of selected IL-4-sensitive genes in blood leukocytes. METHODS: 34 allergic patients suffering from allergic rhinitis (n = 11), atopic eczema (n = 11) and allergic asthma (n = 12) as well as 9 healthy control individuals were recruited. IgE and IL-4 plasma levels were determined by ELISA, and the expression of selected IL-4-sensitive gene products in blood leukocytes was quantified by qRT-PCR. In addition, the fatty acid oxygenase activity of isolated monocytes was measured by RP-HPLC analysis of the arachidonic acid oxygenation products (ex vivo activity assays). RESULTS: We found that plasma levels of IgE and IL-4 were significantly elevated in atopic patients but the degree of elevation was not sufficient to upregulate the expression of the selected IL-4-sensitive genes in circulating leukocytes. Moreover, the arachidonic acid oxygenase activity of blood monocytes was not significantly altered in atopic patients. CONCLUSION: Our data suggest that the IL-4 plasma levels of atopic patients are not high enough to impact the expression of IL-4-sensitive genes.


Assuntos
Hipersensibilidade Imediata/sangue , Hipersensibilidade Imediata/genética , Imunoglobulina E/biossíntese , Interleucina-4/biossíntese , Leucócitos/fisiologia , Adulto , Asma/sangue , Asma/genética , Estudos de Casos e Controles , Dermatite Atópica/sangue , Dermatite Atópica/genética , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Oxigenases/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Rinite Alérgica/sangue , Rinite Alérgica/genética , Regulação para Cima
10.
Medicine (Baltimore) ; 98(20): e15247, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31096432

RESUMO

The aim of the current study was to investigate the expression of long non-coding RNA (lncRNA) antisense non-coding RNA in the INK4 locus (ANRIL) in allergic rhinitis (AR) patients, and to further explore the association of lncRNA ANRIL expression with AR risk, severity, and inflammation.In this case-control study, 96 AR patients and 96 non-atopic obstructive snoring patients who underwent adenoid surgery were consecutively recruited. Disease severity of AR patients was assessed via individual nasal symptom score (INSS) and total nasal symptom score (TNSS). Nasal mucosa samples were collected from AR patients and controls, then lncRNA ANRIL and inflammatory cytokine levels were assessed via quantitative polymerase chain reaction.LncRNA ANRIL expression was increased in AR patients (3.605 [1.763-4.981]) compared with controls (1.183 [0.438-2.985]), and it well distinguished AR patients from controls with an area under curve of 0.746 (95% CI: 0.679-0.814). Correlation analyses revealed that lncRNA ANRIL expression was positively associated with itching score and congestion score, while it was not associated with nasal rhinorrhea score or sneezing score. Besides, lncRNA ANRIL was also positively correlated with TNSS, tumor necrosis factor α, interleukin (IL)-4, IL-6, IL-13, and IL-17, while negatively associated with IL-10 and interferon-γ. And no association of lncRNA ANRIL expression with IL-1ß, IL-5, or IL-8 expression was discovered.LncRNA ANRIL expression correlates with increased AR risk, severity, and inflammation, implying that lncRNA ANRIL might be involved in the pathogenesis of AR.


Assuntos
Loci Gênicos/genética , Inflamação/metabolismo , Mucosa Nasal/metabolismo , RNA Longo não Codificante/genética , Rinite Alérgica/genética , Adolescente , Adulto , Estudos de Casos e Controles , Citocinas/metabolismo , Suscetibilidade a Doenças , Feminino , Humanos , Inflamação/patologia , Interleucina-1beta/metabolismo , Interleucina-5/metabolismo , Interleucina-8/metabolismo , Masculino , Mucosa Nasal/patologia , Fragmentos de Peptídeos/metabolismo , Rinite Alérgica/patologia , Rinite Alérgica/cirurgia , Índice de Gravidade de Doença , Fator de Necrose Tumoral alfa/metabolismo , Adulto Jovem
11.
Biochim Biophys Acta Mol Basis Dis ; 1865(6): 1642-1650, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-30951821

RESUMO

BACKGROUND: Allergic rhinitis is characterized by a remodeling of nasal epithelium. Since the Notch and TGF-ß signaling pathways are known to be involved in cell differentiation and remodeling processes and leptin adipokine has already been identified as a marker for homeostasis in human bronchial and nasal epithelial cells of asthmatics, roles played by these pathways have been investigated for chronic allergic rhinitis. METHODS: The leptin/leptin receptor expression has been investigated in a study with 40 biopsies from allergic (AR, n = 18) and non-allergic (C, n = 22) inferior turbinates, using immunohistochemistry, immunofluorescence staining and RT-PCR. In addition, extracts from in vitro samples prepared from primary cells of inferior turbinates as well as in vitro cultured human nasal epithelial RPMI 2650 cells (ATCC-CCL-30) were also tested for leptin expression and activation of the Notch-1 pathway. RESULTS: With regards to AR, in vivo expression levels of both leptin and its receptor significantly decreased in comparison to C. Furthermore, leptin receptor mRNA was significantly reduced in AR as compared to C. Immunofluorescence showed an apparent co-expression of leptin receptor with Notch-1, which was not seen with TGF-ß. In vitro, in primary turbinate epithelial cells, the expression of leptin receptor and Notch-1 significantly decreased in AR as compared to C. Moreover, in RPMI 2650 cells, leptin receptor expression was shown to be induced by Notch-1 ligand signaling. CONCLUSION: Thus, both the leptin and Notch-1 pathways appear to represent markers for epithelial homeostasis in allergic rhinitis.


Assuntos
Leptina/genética , Mucosa Nasal/metabolismo , Receptor Notch1/genética , Receptores para Leptina/genética , Rinite Alérgica/genética , Adulto , Biópsia , Estudos de Casos e Controles , Linhagem Celular , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Feminino , Regulação da Expressão Gênica , Homeostase/genética , Humanos , Leptina/metabolismo , Masculino , Pessoa de Meia-Idade , Mucosa Nasal/patologia , Cultura Primária de Células , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptor Notch1/metabolismo , Receptores para Leptina/metabolismo , Rinite Alérgica/metabolismo , Rinite Alérgica/patologia , Transdução de Sinais , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo , Conchas Nasais/metabolismo , Conchas Nasais/patologia
12.
Int Immunopharmacol ; 71: 76-83, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30878818

RESUMO

The importance of epigenetics has increased due to identification of its role in the pathophysiology of a number of diseases including allergic rhinitis. Amongst the different epigenetic changes in allergic retinitis, deacetylation of histone proteins by histone deacetylase (HDACs), hypermethylation of DNA by DNA methyltransferases (DNMT) and alteration in post-transcriptional process by the changes in the levels of miRNA are widely studied. Studies conducted related to allergic rhinitis have shown the elevation in the levels of HDAC1, 3 and 11 in the nasal epithelia and HDAC inhibitors have shown effectiveness in decreasing the symptoms of rhinitis. Their beneficial effects are attributed to restoration of the expression of TWIK-related potassium channel-1, correction of cytokine profile along with normalization of Th1/Th2 imbalance. Another epigenetic change due to increase in DNMT activity may induce DNA hypermethylation in CpG sites in the airway epithelial cells and CD4+ T-cells. The reduction in DNA methylation decreases allergic symptoms and normalizes the over-reactive immune system. Mechanistically, allergens may promote the hypermethylation in the promoter region of IFN-γ gene in CD4+ T cells via activation of ERK pathway to decrease the expression of IFN-γ. In allergic rhinitis patients, there is also a downregulation of certain miRNAs including miR-135a, miR-146a, miR-181a, miR-155 and upregulation of miRNA19a. This review discusses the studies describing the epigenetic changes taking place in the host cells in response to allergen along with possible mechanisms.


Assuntos
Epigênese Genética , Rinite Alérgica/genética , Acetilação , Animais , Citocinas/genética , Citocinas/metabolismo , Metilação de DNA , Regulação da Expressão Gênica , Terapia Genética , Humanos , Imunomodulação , MicroRNAs/genética , Rinite Alérgica/terapia , Equilíbrio Th1-Th2
13.
Int J Mol Sci ; 20(4)2019 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-30781605

RESUMO

This study was designed to investigate the potential effects and underlying mechanism of adipose tissue-derived mesenchymal stem cells (MSCs) on allergic inflammation compared to Montelukast as an antileukotriene drug in a rat model of allergic rhinitis (AR). The effect of MSCs was evaluated in albino rats that were randomly divided into four (control, AR, AR + Montelukast, and AR + MSCs) groups. Rats of AR group were sensitized by ovalbumin (OVA) and then challenged with daily nasal drops of OVA diluted in sterile physiological saline (50 µL/nostril, 100 mg/mL, 10% OVA) from day 15 to day 21 of treatment with/without Montelukast (1 h before each challenge) or MSCs I/P injection (1 × 106 MCSs; weekly for three constitutive weeks). Both Montelukast and MSCs treatment started from day 15 of the experiment. At the end of the 5th week, blood samples were collected from all rats for immunological assays, histological, and molecular biology examinations. Both oral Montelukast and intraperitoneal injection of MSCs significantly reduced allergic symptoms and OVA-specific immunoglobulin E (IgE), IgG1, IgG2a and histamine as well as increasing prostaglandin E2 (PGE2). Further analysis revealed that induction of nasal innate cytokines, such as interleukin (IL)-4 and TNF-α; and chemokines, such as CCL11 and vascular cell adhesion molecule-1 (VCAM-1), were suppressed; and transforming growth factor-ß (TGF-ß) was up-regulated in Montelukast and MSCs-treated groups with superior effect to MSCs, which explained their underlying mechanism. In addition, the adipose tissue-derived MSCs-treated group had more restoring effects on nasal mucosa structure demonstrated by electron microscopical examination.


Assuntos
Tecido Adiposo/citologia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Rinite Alérgica/imunologia , Rinite Alérgica/terapia , Animais , Células Cultivadas , Quimiocina CCL11/genética , Quimiocina CCL11/metabolismo , Modelos Animais de Doenças , Interleucina-4/genética , Interleucina-4/metabolismo , Masculino , Mucosa Nasal/patologia , Mucosa Nasal/ultraestrutura , Ratos , Rinite Alérgica/sangue , Rinite Alérgica/genética , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Molécula 1 de Adesão de Célula Vascular/genética , Molécula 1 de Adesão de Célula Vascular/metabolismo
14.
Pediatr Allergy Immunol ; 30(4): 434-442, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30734973

RESUMO

BACKGROUND: Regulatory T cells (Tregs) play central roles in limiting airway allergic inflammation and preventing inappropriate Th2 responses to environmental allergens. This study aims to evaluate the role of miR-181a and miR-155 in the regulation of the differentiation and function of Tregs through both in vivo and in vitro studies. METHODS: The CD4+ T cells and Tregs were purified from peripheral blood mononuclear cells (PBMCs) in allergic rhinitis (AR) children, respectively. The miR-155/181a mimics and inhibitors were transfected into CD4+ T cells and Tregs. The differentiation and function of Tregs were evaluated by flow cytometry and enzyme-linked immunosorbent assay. AR mice models were established, and miR-155/181a mimics or inhibitors were injected through tail vein. The Treg percentage and function from mice were compared among different groups. RESULTS: The miR-181a up-regulated the release of interleukin (IL)-10 and TGF-ß, whereas the miR-155 promoted Treg differentiation in CD4+ T cells. Similarly, we also found that miR-155 promoted Treg proliferation directly through suppressor of cytokine signaling 1 (SOCS1) and sirtuin1 (SIRT1) signaling pathway, whereas miR-181a up-regulated mRNA expression of IL-10 and TGF-ß through phosphatidylinositol 3-OH kinase (PI3K)/Akt pathway. We also found that miR-155/181a affect Treg percentage and function in mice model. CONCLUSION: Our findings suggest that miR-181a and miR-155 were closely correlated with the proliferation and function of Tregs in AR, providing new potential treatment target.


Assuntos
MicroRNAs/genética , Rinite Alérgica/genética , Linfócitos T Reguladores/imunologia , Animais , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Criança , Feminino , Humanos , Tolerância Imunológica , Interleucina-10/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Rinite Alérgica/imunologia , Transdução de Sinais , Fator de Crescimento Transformador beta/metabolismo
15.
Int J Pediatr Otorhinolaryngol ; 120: 58-63, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30771554

RESUMO

OBJECTIVES: Asthma and allergic rhinitis (AR) frequently occur as comorbid diseases of the upper airways. Single-nucleotide polymorphisms (SNPs) in the FCRL3 and FCRL5 genes have recently been shown to be associated with various immune-related disorders. This study evaluated the association of FCRL3 and FCRL5 polymorphisms with asthma and allergic rhinitis (AR) in a Han Chinese population. METHODS: Seven single nucleotide polymorphisms (SNPs) of the FCRL3 and FCRL5 were genotyped in 300 asthmatic children, and 206 healthy unrelated individuals using PCR-restriction fragment length polymorphism (PCR-RFLP) assay. Genotyping was validated by direct sequencing. RESULTS: Our results showed that the frequencies of the rs6692977 CT genotype and T allele within FCRL5 were significantly higher in asthma with comorbid AR compared to healthy controls (Bonferroni-corrected p (Pc) = 3.75 × 10-6; Pc = 0.006, respectively), whereas these of the CC genotype and C allele were significantly lower (Pc = 4.15 × 10-5; Pc = 0.006, respectively). The frequencies of the rs7528684 A allele (Pc = 1.80 × 10-3) and the rs10489678 G allele (Pc = 0.04) within FCRL3 were higher in asthma with comorbid AR than in controls. However, no differences in the tested genetic polymorphisms were detected between asthma and healthy individuals. CONCLUSION: This study identified novel SNPs in FCRL3 and FCRL5 significantly associated with the risk for asthma with comorbid AR in the Chinese population. The genetic variants may play role in the development of the asthma phenotype in children with asthma.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Asma/genética , Receptores Fc/genética , Receptores Imunológicos/genética , Rinite Alérgica/genética , Adolescente , Alelos , Criança , Pré-Escolar , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Lactente , Masculino , Reação em Cadeia da Polimerase/métodos , Polimorfismo de Fragmento de Restrição , Polimorfismo de Nucleotídeo Único , Fatores de Risco
16.
Rev Mal Respir ; 36(2): 135-141, 2019 Feb.
Artigo em Francês | MEDLINE | ID: mdl-30686558

RESUMO

INTRODUCTION: In tropical Africa, allergies are not well documented. The objective of this work was to evaluate, by two methods, the sensitization to mites in children followed for respiratory allergy. METHODS: Skin prick-test and IgE assay by REAST test with 3 mites: Dermatophagoides pteronyssinus (D. pteronyssinus), Dermatophagoides farinae (D. farinae) and Blomia tropicalis (B. tropicalis) were carried out in children from 3 to 15 years followed up for asthma and/or allergic rhinitis. The positive results of the two tests were compared. RESULTS: Of the 130 (100%) children included, all eligible for the assay, 119 (91.5%) had the prick-test. The mean age and sex ratio (M/F) were 7±1 year, and 1.6. The association of rhinitis and asthma was the most frequent and found in 66 (55.6%). The sensitivity frequencies for the prick-test and assay were respectively 79% versus 36.1% for B. tropicalis, 71.4% versus 33.4% for D. pteronyssinus and 38.7% versus 37.8% for D. farinae. A moderate correlation between mean papule diameter and mean IgE concentration was observed. CONCLUSION: In African tropical environments, dust mite sensitization in children followed for respiratory allergy is frequent, with the order of frequency being: B. tropicalis, D. pteronyssinus, and D. farinae. The prick-test had better sensitivity than the assay for its evaluation.


Assuntos
Dermatophagoides farinae/imunologia , Dermatophagoides pteronyssinus/imunologia , Pyroglyphidae/imunologia , Hipersensibilidade Respiratória/diagnóstico , Hipersensibilidade Respiratória/epidemiologia , Adolescente , Animais , Antígenos de Dermatophagoides/imunologia , Asma/diagnóstico , Asma/epidemiologia , Asma/etiologia , Benin/epidemiologia , Criança , Pré-Escolar , Feminino , Humanos , Imunoglobulina E/análise , Masculino , Prevalência , Hipersensibilidade Respiratória/imunologia , Rinite Alérgica/diagnóstico , Rinite Alérgica/epidemiologia , Rinite Alérgica/genética , Testes Cutâneos , Clima Tropical
17.
Am J Rhinol Allergy ; 33(3): 286-293, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30648403

RESUMO

BACKGROUND AND AIMS: The roles of Fas in immune system are multifaceted, and the interaction between Fas receptor and Fas ligand is essential for maintaining the immune tolerance. We aimed to assess the level of the expression of Fas receptor on nasal inferior turbinate mucosa in patients with mild persistent allergic rhinitis (M PAR) and moderate to severe (M/S) PAR and determined the relationship between disease severity and production of Fas. METHODS: A total of 70 patients with M/S PAR, 70 patients with M PAR, and 70 healthy individuals were enrolled in this study. We obtained biopsies of nasal inferior turbinate mucosa from the participants. The expression of Fas mRNA was evaluated by real-time polymerase chain reaction. The presence and location of Fas were determined by immunohistochemistry. The number of eosinophils per field, blood eosinophils, total serum IgE levels, and specific serum IgE levels were measured. Clinical manifestations of patients were assessed by Total Nasal Syndrome Score (TNSS). RESULTS: The expression of Fas in patients with M/S PAR was decreased significantly compared to the control group and patients with M PAR. Local mucosal expression of Fas was correlated with specific IgE, nasal eosinophil count, and TNSS. CONCLUSION: According to the results of this study, there might be a relationship between the expression of Fas receptor on nasal turbinate mucosa and the severity of persistent allergic rhinitis.


Assuntos
Rinite Alérgica/genética , Rinite Alérgica/fisiopatologia , Receptor fas/genética , Receptor fas/metabolismo , Adulto , Animais , Eosinófilos/metabolismo , Feminino , Humanos , Imunoglobulina E/sangue , Imuno-Histoquímica , Contagem de Leucócitos , Masculino , Mucosa Nasal/metabolismo , Mucosa Nasal/patologia , RNA Mensageiro/metabolismo , Rinite Alérgica/metabolismo , Conchas Nasais/metabolismo , Conchas Nasais/patologia , Adulto Jovem
18.
Int Arch Allergy Immunol ; 178(4): 323-332, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30612129

RESUMO

BACKGROUND: While early-life risk factors are known to influence the risk of allergies, the biological mechanisms underlying this observation are unclear. The aim of this study was to examine whether DNA methylation in childhood could underlie the association between early-life risk factors and allergic rhinitis (AR). METHODS: In total, 234 patients, aged 6 years, were recruited, i.e., 114 were patients with AR (AR group) and 120 healthy children without AR (NAR group). The DNA methylation patterns of the IFN-γ promoter regions in CD4+ cells were analyzed using bisulfite sequencing. The percentage of Th1 was investigated by flow cytometry. The relationship among DNA methylation, early-life environment, and AR was examined. RESULTS: After adjusting for several likely confounders, there was a higher likelihood of AR in children who had mothers with allergies than in children who had nonallergic mothers (OR = 5.19; 95% CI 1.18-29.41), in children who were born in autumn or winter than in children who were born in the summer or spring (OR = 2.69; 95% CI 1.34-5.40), and in children who lived with indoor carpet or wallpaper than in children who lived without indoor carpet or wallpaper (OR = 4.14; 95% CI 2.05-8.30). Compared to the NAR group, the AR group had higher mean methylation levels of the promoter region in IFN-γY, and lower numbers of IFN-γ+CD4+ cells were associated with autumn-winter birthdates. The season of birth had an indirect effect on AR at 6 years, which was mediated by the mean IFN-γ promoter methylation level. CONCLUSIONS: This study suggests that early-life environments affect AR, and this is supported by the finding of IFN-γY methylation as a mediator of the effect of an individual's season of birth on AR.


Assuntos
Metilação de DNA , Interferon gama/genética , Rinite Alérgica/genética , Linfócitos T CD4-Positivos/imunologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Regiões Promotoras Genéticas , Rinite Alérgica/imunologia , Estações do Ano
19.
Methods ; 152: 48-54, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-29906503

RESUMO

Chronic inflammatory diseases can be particularly challenging to diagnose and characterize, as inflammatory changes in tissue may not be present in blood. There is a crucial need to develop non-invasive biomarkers that would be useful in diagnosing disease and selecting medical therapies. For example, there are no blood tests to diagnose asthma, a common inflammatory lung disease. MicroRNA (miRNA) expression profiling in blood is emerging as a potentially sensitive and useful biomarker of many diseases. In particular, we have characterized a cost-effective PCR-based array technology to measure and profile circulating miRNAs in the plasma of patients with allergic rhinitis and asthma. Here, we describe the methods to isolate, quantify, and analyze miRNAs in the plasma of human subjects as well as ways to determine their diagnostic utility.


Assuntos
Asma/genética , MicroRNAs/isolamento & purificação , Reação em Cadeia da Polimerase/métodos , Rinite Alérgica/genética , Biomarcadores/química , Humanos , MicroRNAs/química
20.
J Cell Biochem ; 120(1): 164-170, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30168182

RESUMO

H1-antihistamine has been shown to be effective in treating patients with allergic rhinitis (AR), but its mechanism is still uncertain. We investigated effects of histamine H1 receptor (HRH1) gene polymorphisms on the efficacy of oral H1-antihistamine in perennial patients with AR caused by mites in the Chinese Han population for the first time. A total of 224 Han Chinese patients with AR and 165 Han Chinese healthy volunteers were selected. Genotype and allele frequency distribution of -17C/T in HRH1 gene in patients with AR, serum levels of eosinophil cationic protein (ECP), total immunoglobulin E (IgE), and specific IgE were detected. The clinical symptoms of patients with AR were evaluated with visual analogue scale (VAS). Direct counting method was applied to calculate genotype and allele frequencies. Higher levels of serum ECP and total IgE were shown in the AR group. Moreover, patients with CT, TT, or CT+TT genotype increased the risk of AR incidence in the in the -17C/T site of HRH1, and CC genotype and CT+TT genotype were associated with gender, asthma, VAS score, total IgE level, and specific IgE level in patients with AR. In addition, oral administration of H1-antihistamines improves clinical symptoms of patients with AR. At last, patients with the CC genotype showed the increased efficacy of H1-antihistamines in patients with AR. Our study provides evidence that HRH1 gene polymorphisms may correlate with oral H1-antihistamine efficacy for the treatment of patients with AR, which can be used as a biological indicator of the prediction of therapeutic efficacy of patients with AR.


Assuntos
Biomarcadores Ambientais/genética , Antagonistas dos Receptores Histamínicos H1/uso terapêutico , Ftalazinas/uso terapêutico , Polimorfismo de Nucleotídeo Único , Receptores Histamínicos H1/genética , Rinite Alérgica/tratamento farmacológico , Rinite Alérgica/genética , Administração Oral , Adolescente , Adulto , Asma/genética , Criança , China , Proteína Catiônica de Eosinófilo/sangue , Feminino , Frequência do Gene/genética , Genótipo , Antagonistas dos Receptores Histamínicos H1/administração & dosagem , Humanos , Imunoglobulina E/sangue , Masculino , Pessoa de Meia-Idade , Ftalazinas/administração & dosagem , Fatores Sexuais , Resultado do Tratamento , Adulto Jovem
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