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1.
Chem Biol Interact ; 315: 108874, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31669322

RESUMO

Allergic rhinitis (AR) is a type I hypersensitivity immune response and is a common chronic allergic respiratory disorder characterized by one or more nasal symptoms. Despite many studies on AR therapy, the drugs of treatment for AR remain limited in effect. In the present study, we aimed to elucidate the effects of saikosaponin A (SSA) on nasal inflammation, T helper (Th)2 and Th17 cytokines, retinoic acid-related orphan nuclear receptor (ROR)-γt, signal transducer and activator of transcription (STAT)3, and nuclear factor (NF)-κB signalings in ovalbumin (OVA)-induced AR mice model. OVA-induced AR mice exhibited increase in nasal symptoms, histological alteration, OVA-specific immunoglobulin (Ig)E/IgG1, ROR-γt, STAT3 and NF-κB signalings. However, the administration of SSA significantly decreased allergic symptoms including nasal rubbing and sneezing. Additionally, histological alterations such as mucosa layer thickness, goblet cell hyperplasia, eosinophils and mast cell infiltration in nasal tissues dramatically improved by treatment with SSA. Also, SSA treatment decreased the levels of OVA-specific IgE/IgG1 in serum and the levels of Th2 and Th17 cytokines such as interleukin (IL)-6 and IL-17 in nasal lavage fluid (NALF). Moreover, SSA inhibited the activation of transcription factor ROR-γt, STAT3 and phosphorylated STAT3 in both NALF and lung. Futher, SSA could also significantly inhibit the expressions of NF-κB p65 and phosphorylated NF-κB p65 in NALF and lung. These present results suggested that SSA may attenuate OVA-induced allergic rhinitis through regulating the expression of IL-6/ROR-γt/STAT3/IL-17/NF-κB signaling. The results indicate that SSA may be used as a therapeutic candidate for allergic rhinitis disease.


Assuntos
Inflamação/tratamento farmacológico , Inflamação/metabolismo , Mucosa Nasal/efeitos dos fármacos , Ácido Oleanólico/análogos & derivados , Rinite Alérgica/tratamento farmacológico , Rinite Alérgica/metabolismo , Saponinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Animais , Citocinas/metabolismo , Modelos Animais de Doenças , Imunoglobulina E/metabolismo , Imunoglobulina G/metabolismo , Interleucina-17/metabolismo , Interleucina-6/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/metabolismo , Mucosa Nasal/metabolismo , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Ácido Oleanólico/farmacologia , Ovalbumina/farmacologia , Rinite Alérgica/induzido quimicamente , Fator de Transcrição STAT3/metabolismo , Células Th17/efeitos dos fármacos , Células Th17/metabolismo , Células Th2/efeitos dos fármacos , Células Th2/metabolismo
2.
Life Sci ; 236: 116901, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31610206

RESUMO

AIMS: Allergic rhinitis is a global cause of disability, characterized by airway inflammation. Sumatriptan is a 5-hydroxytryptamine 1B/1D (5HT1B/1D) agonist used as a treatment for migraine headaches. Activation of 5HT1B/1D receptors can inhibit the release of neuropeptides and inhibit the inflammation cascades. This study investigated the effect of sumatriptan on ovalbumin-induced allergic rhinitis model in mice and the role of nitric oxide. METHODS: Female Balb/c mice were sensitized by intraperitoneal ovalbumin and challenged by intranasal ovalbumin. Mice received sumatriptan in doses 3, 10, 30 µg/kg intraperitoneally, 30 min before the last ovalbumin challenge. KEY FINDINGS: Intraperitoneal injection of sumatriptan significantly decreased the nasal scratching, IL-4 and serum IgE levels of allergic mice, but it increased IFNγ levels. Histopathological analysis showed that the number of eosinophils was significantly elevated in nasal mucosa of ovalbumin-induced allergic mice, while sumatriptan treatment significantly reduced the number of eosinophils. GR-127935, a selective 5-HT1B/1D-receptor antagonist, reversed the anti-allergic effects of sumatriptan. Acute administration of l-NAME, a non-specific inhibitor of nitric oxide synthase, along with sumatriptan attenuated the anti-allergic effects of sumatriptan but chronic administration of l-NAME did not affect the influences of sumatriptan. Furthermore, sumatriptan decreased the inducible nitric oxide synthase (iNOS) protein expression in allergic mice, but it did not change the concentration of eNOS protein. SIGNIFICANCE: This study shows that sumatriptan administration is associated with anti-allergic effects which are through 5HT1B/1D receptors. Decrease in iNOS expression and changes in T-helper 1&2 cytokines levels may indicate the involvement of inducible NOS and inflammation.


Assuntos
Óxido Nítrico Sintase Tipo II/metabolismo , Óxido Nítrico/metabolismo , Ovalbumina/toxicidade , Rinite Alérgica/prevenção & controle , Agonistas do Receptor 5-HT1 de Serotonina/farmacologia , Transdução de Sinais/efeitos dos fármacos , Sumatriptana/farmacologia , Animais , Modelos Animais de Doenças , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Rinite Alérgica/induzido quimicamente , Rinite Alérgica/metabolismo , Rinite Alérgica/patologia
3.
Artigo em Chinês | MEDLINE | ID: mdl-31623032

RESUMO

SummaryThe binding of IL-33 and its receptor ST2 plays a key role in the development of cardiovascular diseases, chronic inflammation, allergic diseases and fibrosis related diseases. The study of the relationship between IL-33/ST2 signaling pathway and these diseases may provide new ideas and methods for the diagnosis and treatment of diseases. Although many high-quality studies have been done on the role of IL-33/ST2 signaling pathway in the pathogenesis of allergic rhinitis, there is still a lack of comprehensive and clear explanation. This paper reviews the role of IL-33/ST2 signaling pathway in the pathogenesis of allergic rhinitis on the basis of literature review. This signaling pathway can be used to guide the treatment of allergic rhinitis in theory.


Assuntos
Interleucina-33/metabolismo , Rinite Alérgica/metabolismo , Humanos , Inflamação , Proteína 1 Semelhante a Receptor de Interleucina-1 , Transdução de Sinais
4.
Artigo em Chinês | MEDLINE | ID: mdl-31623047

RESUMO

Objective:To analyze the relationship and mechanism of mast cell with allergic rhinitis and nasal polyps. Method:From January 2018 to June 2018, all the inpatients in Otolaryngology Department were examined by nasal endoscopy and CT before operation. They were divided into three groups: 30 patients with allergic rhinitis(AR group) and 30 patients with nasal polyps(NP group) as the experimental group; 30 patients with nasal septum correction after partial inferior turbinectomy alone as the control group(N group). Clinical data, peripheral blood and nasal mucosa were collected. The percentage of eosinophils in peripheral blood was detected by automatic hematology analyzer. The levels of anti-IgE antibody, FcεRIα and anti-FcεRIα antibody in serum were detected by ELISA. The levels of serum IgE were detected by velocity scattering turbidimetry. HE was used to observe the histopathological changes in the three groups. Immunohistochemical method was used to analyze the expression of tryptase and FcεRIα in the experimental group and the control group. Result:The percentage of eosinophils, IgE, anti-IgE antibody, FcεRIα and anti-FcεRIα antibodies in AR group were significantly higher than those in control group(P<0.05); the percentage of eosinophils, FcεRIα and anti-FcεRIα antibodies in NP group were significantly higher than those in healthy control group(P<0.05). There was no significant difference in IgE and anti-IgE antibodies among three groups(P>0.05). The eosinophil percentage, IgE and anti-IgE antibody levels in AR group were significantly higher than that in NP group(P<0.05); there were no differences in FcεRIα and anti-FcεRIα antibody levels between AR group and NP group(P>0.05); There was no significant difference in eosinophil infiltration between the two groups; The brown tryptase-positive mast cells and FcεRIα-positive mast cells were found in the submucosa and interstitium of nasal mucosa. Conclusion:The high expression of FcεRIα and its antibody in the serum of patients with allergic rhinitis and nasal polyps indicated that this antibody system was involved in the occurrence and development of allergic rhinitis and nasal polyps. Local allergy with mast cells as the core might play an important role in the occurrence and development of nasal polyps. The possible role of mast cells in the formation of nasal polyps and the specific mechanism deserve further study.


Assuntos
Mastócitos/metabolismo , Pólipos Nasais/metabolismo , Rinite Alérgica/metabolismo , Eosinófilos , Humanos , Imunoglobulina E , Mucosa Nasal
5.
Allergol. immunopatol ; 47(5): 411-416, sept.-oct. 2019. tab, graf
Artigo em Inglês | IBECS | ID: ibc-186514

RESUMO

Background: Some studies have showed that seasonality is an important determinant of vitamin D (vitD) status. Objective: We evaluated whether there are differences in individual trends of serum vitD level over one year in asthmatic and rhinitic children. Materials and methods: Ninety-two asthmatic and rhinitic paediatric patients were followed up for one year and their serum vitD level was detected at three-month intervals, once in each season. Results: We observed higher vitD levels at the end of summer and lower at the end of winter. However, the individual seasonal trend was very variable and unpredictable. If it is true that in a given season the majority of patients followed one direction (increase or decrease of serum vitD levels), nevertheless a substantial percentage behaved differently and unpredictably. For example, at the end of spring, 70% of patients showed an increase in serum vitD levels, but 30% showed a decrease. In addition, five individuals had a value ≥ 50 ng/ml in September and showed serum vitD levels ≥ 30ng/ml throughout the year; 16 patients presented vitD value ≥ 40 ng/ml in September and always had ≥ 20 ng/ml in the other months. Conclusions: The wide and unpredictable variability of the individual trend of serum vitD levels should be taken into account before deciding whether or not a drug supplementation is appropriate


No disponible


Assuntos
Humanos , Masculino , Feminino , Criança , Adolescente , Asma/metabolismo , Rinite Alérgica/metabolismo , Estações do Ano , Vitamina D/sangue , Variação Biológica da População , Suplementos Nutricionais , Seguimentos
6.
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
7.
Int J Pediatr Otorhinolaryngol ; 126: 109603, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31369971

RESUMO

OBJECTIVE: To determine whether the measurement of exhaled nitric oxide (eNO) can help distinguish children with allergic rhinitis (AR) from healthy controls and whether eNO in children with AR correlates with disease severity. METHODS: From August 2015 to 2016, children aged 5-15 years of age grouped into those with allergic rhinitis (n = 40) and those classified as healthy control subjects (n = 40) had exhaled nitric oxide (eNO) levels measured. The eNO level was additionally compared to the patient's clinical disease severity according to the ARIA (Allergic Rhinitis and its Impact on Asthma) classification. RESULTS: Mean eNO in children with AR (12.64 ±â€¯14.67 ppb) was significantly higher than that in the healthy control group (7.00 ±â€¯6.33 ppb) (p-value = 0.046). In the persistent AR group (17.11 ±â€¯18.40 ppb), eNO level was significantly higher than individuals in the intermittent AR group (8.59 ±â€¯8.88 ppb, p-value = 0.024) and the healthy control group (7.00 ±â€¯6.33 ppb, p-value = 0.008). Among children with AR, eNo was not significantly different with relationship to gender, age, weight and passive smoking exposure. CONCLUSIONS: Exhaled nitric oxide may be elevated in children with AR that do not have concomitant asthma. This suggests exhaled nitric oxide may show utility as a parameter to monitor the severity of allergic rhinitis and to monitor the efficacy of the treatment. Physicians should consider comorbid AR when utilizing exhaled nitric oxide as a monitoring parameter in the treatment of asthma.


Assuntos
Expiração , Óxido Nítrico/metabolismo , Rinite Alérgica/metabolismo , Índice de Gravidade de Doença , Adolescente , Testes Respiratórios , Estudos de Casos e Controles , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Masculino , Rinite Alérgica/diagnóstico
8.
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
9.
Mol Immunol ; 114: 362-368, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31450181

RESUMO

Madi-Ryuk (MDR) is a traditional Korean medicine and it has been widely used in Korea to treat arthritis and we previously reported the anti-allergic inflammatory effect of MDR in vitro model. However, therapeutic evidence of MDR on in vivo model of allergic inflammatory reaction has not yet been demonstrated. The research purpose was to investigate the efficacy of MDR and its active ingredient tannic acid (TA) in ovalbumin (OVA)-induced AR mice model. OVA-challenged AR mice orally medicated MDR or its active ingredient TA daily for ten days. In mice having a AR, MDR and TA prominently diminished number of rubs and levels of histamine, IgE, thymic stromal lymphopoietin, interleukin (IL)-1ß, IL-4, IL-5, IL-13, IL-33, and tumor necrosis factor-α. In addition, protein expression levels and activities of caspase-1 were declined by oral medication of MDR and TA. Decline in levels of macrophage inflammatory protein-2 and intercellular adhesion molecules-1 and reduction in penetrations of inflammatory cells into inflamed tissue were also noted in MDR and TA groups. Taken together, identification of MDR effect in preclinical models suggests that MDR may be a therapeutic drug for the treatment and prevention of AR.


Assuntos
Anti-Inflamatórios/farmacologia , Rinite Alérgica/tratamento farmacológico , Taninos/farmacologia , Animais , Caspase 1/metabolismo , Quimiocina CXCL2/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Eosinófilos/efeitos dos fármacos , Eosinófilos/metabolismo , Histamina/metabolismo , Imunoglobulina E/metabolismo , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Interleucina-1beta/metabolismo , Medicina Tradicional Coreana/métodos , Camundongos , Camundongos Endogâmicos BALB C , Mucosa Nasal/efeitos dos fármacos , Mucosa Nasal/metabolismo , Ovalbumina/farmacologia , Rinite Alérgica/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
10.
Ann Otol Rhinol Laryngol ; 128(6_suppl): 26S-35S, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31092040

RESUMO

OBJECTIVE: Sublingual immunotherapy has been considered to be a painless and effective therapeutic treatment of patients with allergic rhinitis. Its mechanism of action has been elucidated, but there are still controversies among many reports between clinical efficacy and laboratory data. Therefore, its mechanism of action needs to be investigated further by using promising animal models such as rodents and monkeys. MATERIALS AND METHODS: Bearing this in mind, in our present study, we successfully constructed an effective murine model for sublingual immunotherapy (SLIT) in allergic rhinitis in which mice were sublingually administered ovalbumin (OVA), followed by intraperitoneal (ip) sensitization and intranasal (i.n.) challenge of OVA. RESULTS: To summarize our experimental data, nasal symptoms such as sneezing and nasal rubbing of sublingually treated mice were significantly attenuated in accordance with lower specific IgE antibodies in sera. Histological analysis of eosinophil recruitment in nasal mucosae reveals less allergic inflammation in sublingually treated mice. Interleukin-10 (IL-10) production and IL-10-specific mRNA gene expression of cultured submandibular lymph node (SMLN) cells with OVA, obtained from sublingually treated mice, were significantly higher than those of mice without sublingual treatment. CONCLUSION: These results demonstrate that sublingually introduced antigens can actually attenuate nasal symptoms in a murine allergic rhinitis model upon allergen exposures. Furthermore, our immunological data might indicate an important role of IL-10 producing T cells in SMLN to control nasal allergic reaction.


Assuntos
Interleucina-10/metabolismo , Linfonodos/metabolismo , Rinite Alérgica/terapia , Imunoterapia Sublingual , Linfócitos T/metabolismo , Animais , Modelos Animais de Doenças , Feminino , Camundongos , Rinite Alérgica/complicações , Rinite Alérgica/metabolismo , Espirro
11.
EBioMedicine ; 43: 587-593, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31056472

RESUMO

BACKGROUND: Autoimmunity and allergy have been associated with decreased number and function of regulatory T-cells (Tregs) and low interleukin-2 (IL-2) levels. We aimed to investigate if the release of IL-2 from peripheral blood mononuclear cells (PBMCs) stimulated with pathogenic airway bacteria was associated with development of allergy-outcomes in early childhood. METHODS: PBMCs were isolated at age 6 months in 331 infants from the Copenhagen Prospective Studies on Asthma in Childhood 2000 (COPSAC2000) mother-child cohort, and subsequently stimulated with H. influenzae, M. catarrhalis and S. pneumoniae in in vitro cultures. Levels of cytokines (IL-2, IL-10, IFN-γ, TNF-α, IL-5, IL-13 and IL-17A) were determined in the supernatant by electrochemiluminescence immunoassays. The immune profiles were analyzed for association with development of total-IgE, allergic sensitization and rhinitis during the first 7 years of life using regression models and principal component analysis (PCA). FINDINGS: An attenuated IL-2 response to stimulation with H. influenzae (p = 0∙011) and M. catarrhalis (p = 0∙027) was associated with elevated total-IgE at age 7, which was confirmed in a multivariate PCA model including all cytokine measurements (PC2, p = 0∙032). An immune profile with both reduced IL-2 and elevated IL-5 was associated with increased risk of allergic rhinitis (PC3, p = 0∙038). We found no associations with development of allergic sensitization. INTERPRETATION: A reduced IL-2 response from PBMCs exposed to common pathogenic airway bacteria at age 6 months was associated with elevated total-IgE and allergic rhinitis during the first 7 years of life. These findings suggest that suppressed Treg activity in early life may herald onset of allergy in early childhood, which could be a target for low-dose IL-2 trials in the future. FUND: COPSAC is funded by private and public research funds all listed on www.copsac.com.


Assuntos
Bactérias/imunologia , Imunoglobulina E/imunologia , Interleucina-2/metabolismo , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Rinite Alérgica/etiologia , Rinite Alérgica/metabolismo , Fatores Etários , Alérgenos/imunologia , Infecções Bacterianas/complicações , Infecções Bacterianas/imunologia , Infecções Bacterianas/microbiologia , Estudos de Coortes , Citocinas/metabolismo , Suscetibilidade a Doenças , Feminino , Humanos , Imunização , Imunoglobulina E/sangue , Imunofenotipagem , Lactente , Recém-Nascido , Masculino , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo
13.
Artigo em Chinês | MEDLINE | ID: mdl-30970402

RESUMO

Objective:To investigate the expression of microtubuleassociated protein 1 light chain 3 beta(LC3) and eosinophil cationic protein in allergic rhinitis(AR) for further understanding of the pathogenesis of AR. Method: Twenty cases of normal nasal mucosa and 20 cases of AR nasal mucosa were collected. Histological changes of nasal mucosa were examined by hematoxylin and eosin(HE) staining. The expression of LC3 and ECP were measured by immunohistochemistry(IHC) and Western Blot(WB). Result: The tissue samples demonstrated a large number of eosinophils and lymphocytes infiltration in AR. IHC revealed that LC3 and ECP expression were higher in AR than in normal nasal mucosa(P<0.05). WB also showed that the relative expression levels of protein expression of LC3 and ECP were greater in AR than in controls. The expression level of LC3 was positively correlated with that of ECP protein in AR. Conclusion: LC3 and ECP were upregulated and positively correlated in AR, indicating that autophagy plays an important role in the toxicity of allergic rhinitis , which provides theoretical basis for the precise treatment of AR.


Assuntos
Proteína Catiônica de Eosinófilo , Proteínas Associadas aos Microtúbulos , Rinite Alérgica , Autofagia , Proteína Catiônica de Eosinófilo/metabolismo , Eosinófilos , Humanos , Contagem de Leucócitos , Proteínas Associadas aos Microtúbulos/metabolismo , Mucosa Nasal , Rinite Alérgica/metabolismo
14.
Artigo em Chinês | MEDLINE | ID: mdl-30991778

RESUMO

Objective: To explore the effect of neurokinin-1 receptor small interfering RNA (NK-1R-siRNA) on the expression of inflammation factors in allergic rhinitis (AR). Methods: Twenty-four male SD rats were divided into three groups randomly (by random number table methord): NK-1R-siRNA group, negative control siRNA (NC-siRNA) group and saline group, with 8 rats in each group. SD rats were sensitized and challenged with ovalbumin (OVA) to induce AR. The rats were treated intranasally with NK-1R-siRNA, NC-siRNA or saline before and during the challenge period. The AR symptoms were observed. The levels of OVA-specific IgE were measured by enzyme-linked immunosorbent assay (ELISA). The levels of NK-1R expression in the nasal mucosal tissues were determined by real time PCR (RT-PCR) and immunohistochemistry. Antibody array was used in studying the expression of inflammation cell factors in nasal mucosa. SPSS 11.0 software was used for one-factor analysis of variance. Results: Compared with saline group, AR symptoms relived significantly in NK-1R-siRNA group (nose rubbing (31.4±8.9)/15 min vs (69.5±17.9)/15 min, sneezing (7.2±1.9)/15 min vs (23.7±9.2)/15 min, nasal secretions (7.1±2.3) mg vs (24.1±4.4) mg, t value was 38.100, 17.125, 16.837, respectively, all P<0.01), and the level of serum OVA-specific IgE was also reduced ((8.56±0.73) ng/ml vs (18.05±1.22) ng/ml, t=9.787, P<0.01). The RT-PCR and immunohistochemistry results showed that the expression of NK-1R in nasal mucosa of NK-1R-siRNA group was remarkably reduced than that of the NC-siRNA group and saline group. After the treatment of NK-1R-siRNA, the expression of interleukin (IL) 1α, IL-1ß, IL-4, IL-6 and IL-13 decreased, while the interferon-γ (IFN-γ) and IL-10 increased. Conclusion: NK-1R-siRNA could regulate the release of inflammation factors in AR nasal mucosa, thus relive the allergic inflammation.


Assuntos
Interleucinas/metabolismo , RNA Interferente Pequeno/farmacologia , Receptores da Neurocinina-1/genética , Rinite Alérgica/metabolismo , Rinite Alérgica/terapia , Animais , Modelos Animais de Doenças , Interferon gama/metabolismo , Masculino , Mucosa Nasal/química , Mucosa Nasal/imunologia , Ovalbumina , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Receptores da Neurocinina-1/análise , Receptores da Neurocinina-1/metabolismo , Rinite Alérgica/etiologia
15.
Allergol Immunopathol (Madr) ; 47(5): 411-416, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30940418

RESUMO

BACKGROUND: Some studies have showed that seasonality is an important determinant of vitamin D (vitD) status. OBJECTIVE: We evaluated whether there are differences in individual trends of serum vitD level over one year in asthmatic and rhinitic children. MATERIALS AND METHODS: Ninety-two asthmatic and rhinitic paediatric patients were followed up for one year and their serum vitD level was detected at three-month intervals, once in each season. RESULTS: We observed higher vitD levels at the end of summer and lower at the end of winter. However, the individual seasonal trend was very variable and unpredictable. If it is true that in a given season the majority of patients followed one direction (increase or decrease of serum vitD levels), nevertheless a substantial percentage behaved differently and unpredictably. For example, at the end of spring, 70% of patients showed an increase in serum vitD levels, but 30% showed a decrease. In addition, five individuals had a value ≥50ng/ml in September and showed serum vitD levels ≥30ng/ml throughout the year; 16 patients presented vitD value ≥40ng/ml in September and always had ≥20ng/ml in the other months. CONCLUSIONS: The wide and unpredictable variability of the individual trend of serum vitD levels should be taken into account before deciding whether or not a drug supplementation is appropriate.


Assuntos
Asma/metabolismo , Rinite Alérgica/metabolismo , Estações do Ano , Vitamina D/sangue , Adolescente , Variação Biológica da População , Criança , Suplementos Nutricionais , Feminino , Seguimentos , Humanos , Masculino
16.
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
17.
Eur Arch Otorhinolaryngol ; 276(6): 1655-1661, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30848348

RESUMO

PURPOSE: Epithelial thymic stromal lymphopoietin (TSLP) promotes Th2 inflammatory responses through induction of OX40 ligand (OX40L) on dendritic cells in allergic rhinitis (AR). Emerging evidence supports the important role of histamine H4 receptor (H4R) in allergic inflammation. This study aimed to investigate the effects of H4R in Th2-cytokine profile mediated by TSLP in AR. METHODS: Human nasal epithelial cells (HNECs) from AR patients were stimulated with histamine in the presence or absence of H4R agonist (4-methylhistamine, 4-MH) and antagonist (NJ7777120, JNJ) or H1R agonist (2-pyridylethylamine). TSLP protein was measured by Western blotting and ELISA. To further elucidate the role of H4R in the in vivo situation of experimental AR, rats were sensitized and treated with JNJ or 4-MH. TSLP and OX40 ligand (OX40L) in the nasal mucosa were assayed by Western blotting. Th2 cytokines including interleukin-4, 5 and 13 in nasal lavage fluids were detected by ELISA. RESULTS: Histamine alone did not induce TSLP production by HNECs. The pre-incubation with 4-MH prior to histamine promoted TSLP expression, which was inhibited by the stimulation with JNJ prior to histamine and 4-MH. The pre-incubation with 2-pyridylethylamine before histamine stimulation had no impact on TSLP production. In AR rats, the levels of TSLP and OX40L protein were increased as well as Th2 cytokines, which was further up-regulated by 4-MH treatment, while JNJ treatment attenuated these effects. CONCLUSIONS: H4R activation induced TSLP production by HNECs, which up-regulated OX40L expression in the nasal mucosa of sensitized rats. These factors promoted Th2-cytokine profile in AR.


Assuntos
Citocinas/imunologia , Inflamação/metabolismo , Ligante OX40 , Receptores Histamínicos H4 , Rinite Alérgica , Células Th2 , Animais , Citocinas/metabolismo , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/metabolismo , Histamínicos/farmacologia , Humanos , Mucosa Nasal/efeitos dos fármacos , Mucosa Nasal/imunologia , Mucosa Nasal/metabolismo , Ligante OX40/imunologia , Ligante OX40/metabolismo , Ratos , Receptores Histamínicos H4/agonistas , Receptores Histamínicos H4/antagonistas & inibidores , Receptores Histamínicos H4/imunologia , Rinite Alérgica/imunologia , Rinite Alérgica/metabolismo , Células Th2/imunologia , Células Th2/metabolismo , Regulação para Cima
18.
Artigo em Chinês | MEDLINE | ID: mdl-30813699

RESUMO

Objective:To observe the effect of 18ß-sodium glycyrrhetinic acid(18ß-SGA) on the expression of TNF-α in nasal mucosa of rats with allergic rhinitis(AR), and explore the intervention mechanism of 18ß-SGA on AR. Method:One hundred and six SPF-level Wistar rats were randomly divided into control group, AR group, budesonide group, 18ß-SGA low dose group and high dose group. After the AR rat model was constructed by ovalbumin, the rats were given drug intervention and sacrificed after 2 and 4 weeks of intervention. The nasal mucosa of the rats was taken for immunohistochemical staining, RT-qPCR and Western-blotting to localize and quantify the expression of TNF-α. Result:By immunohistochemistry, Western-blotting and RT-PCR, TNF-α was mainly found in the columnar epithelium, vascular endothelium, glandular and some inflammatory cytoplasm of nasal mucosa. And the expression of TNF-α in the nasal mucosa of AR rats was significantly increased than the normal group at the protein and mRNA levels (P<0.01). After intervention with different doses of 18ß-SGA, the expression of TNF-α was significantly decreased (P<0.01), especially after 4 weeks of 18ß-SGA low dose group(P<0.01). Conclusion:Different doses of 18ß-SGA have therapeutic effects on AR, and its mechanism of action may be related to the inhibition of TNF-α expression.


Assuntos
Anti-Inflamatórios , Ácido Glicirretínico , Rinite Alérgica , Fator de Necrose Tumoral alfa , Animais , Anti-Inflamatórios/farmacologia , Modelos Animais de Doenças , Ácido Glicirretínico/farmacologia , Mucosa Nasal , Distribuição Aleatória , Ratos , Ratos Wistar , Rinite Alérgica/tratamento farmacológico , Rinite Alérgica/metabolismo , Sódio , Fator de Necrose Tumoral alfa/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo
19.
Artigo em Chinês | MEDLINE | ID: mdl-30704168

RESUMO

Objective: To investigate the regulation of IL-25 on type Ⅱ innate lymphoid cells (ILC2s) activation in the pathogenesis of allergic fungal rhinosinusitis (AFRS). Methods: Nasal mucosa tissues were collected from 16 AFRS patients and 12 patients, who underwent nasal endoscopic surgery for cerebrospinal rhinorrhea or skull base benign tumor during the period from June 2016 to June 2017 in Department of Rhinology, the First Affiliated Hospital of Zhengzhou University. Firstly, flow cytometry was used to detect ILC2s in nasal mucosa of both groups. Secondly, the expression of IL-25, IL-5 and IL-13 in nasal mucosa was detected by immunofluorescence and/or Western Blot assay. Finally, fungal extracts, IL-25 and glucocorticoids were used to stimulate nasal mucosal epithelial cells and tissues in vitro respectively to detect the regulatory effect of IL-25 on ILC2s. SPSS 16.0 software was used to analyze the data. Results: The prevalence of ILC2s in nasal tissues was higher in patients with AFRS than those of the control group ((3.85±1.52)%(Mean±SD) vs (0.32±0.10)%, U=9.00, P<0.05). There was a positive correlation between the prevalence of ILC2s and the number of eosinophils in nasal mucosa of patients with ARFS (r=0.80, P<0.05). The expression of IL-25, IL-5 and IL-13 in nasal mucosa epithelium of AFRS group was significantly higher than that of the control group (0.49±0.13 vs 0.23±0.09, 0.23±0.05 vs 0.10±0.04, 0.31±0.08 vs 0.14±0.07, t value was 5.90, 7.21, 5.69, respectively, all P<0.05). Fungal stimulation enhanced the expression of IL-25 protein in nasal epithelial cells of both groups (0.67±0.19 vs 0.25±0.12 (AFRS group), 0.62±0.17 vs 0.27±0.16 (control group), q value was 8.65, 9.26, respectively, all P<0.05). In the IL-25 stimulated nasal mucosa at a concentration of 1, 10 and 100 ng/ml, the expression level of retinoid acid-related orphan receptor α (RORα) mRNA was 2.07±1.53, 5.06±0.93, 7.38±2.30, respectively; the expression level of GATA binding protein 3 (GATA3) mRNA was 3.58±1.29, 6.14±1.55, 7.64±2.28, respectively; the expression level of IL-5 protein was 0.21±0.06, 0.32±0.06, 0.38±0.10, respectively; the expression level of IL-13 was 0.52±0.13, 0.69±0.22, 0.82±0.21, respectively, which were significantly higher than that in the unstimulated nasal mucosa (1.00±0.00, 1.00±0.00, 0.11±0.05, 0.35±0.15, F value was 63.45, 59.27, 49.35, 20.20, respectively, all P<0.05). The up-regulation could be inhibited by dexamethasone (F value was 89.20, 92.47, 99.63, 49.82, respectively, all P<0.05). Conclusions: Epithelial-derived IL-25 up-regulates the expression of IRC2s-dependent transcription factors RORα and GATA3 mRNA, which are positively correlated with elevated IL-13 and IL-5 expression levels in tissues, may be involved in AFRS inflammatory response, and are inhibited by glucocorticoids.


Assuntos
Interleucina-17/metabolismo , Ativação Linfocitária , Rinite Alérgica/etiologia , Sinusite/etiologia , Eosinófilos/citologia , Fator de Transcrição GATA3/metabolismo , Humanos , Interleucina-13/metabolismo , Interleucina-17/imunologia , Interleucina-5/metabolismo , Linfócitos , Mucosa Nasal/citologia , Mucosa Nasal/metabolismo , Membro 1 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Rinite Alérgica/metabolismo , Sinusite/metabolismo
20.
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
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