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2.
Cell ; 182(2): 429-446.e14, 2020 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-32526206

RESUMO

The mode of acquisition and causes for the variable clinical spectrum of coronavirus disease 2019 (COVID-19) remain unknown. We utilized a reverse genetics system to generate a GFP reporter virus to explore severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogenesis and a luciferase reporter virus to demonstrate sera collected from SARS and COVID-19 patients exhibited limited cross-CoV neutralization. High-sensitivity RNA in situ mapping revealed the highest angiotensin-converting enzyme 2 (ACE2) expression in the nose with decreasing expression throughout the lower respiratory tract, paralleled by a striking gradient of SARS-CoV-2 infection in proximal (high) versus distal (low) pulmonary epithelial cultures. COVID-19 autopsied lung studies identified focal disease and, congruent with culture data, SARS-CoV-2-infected ciliated and type 2 pneumocyte cells in airway and alveolar regions, respectively. These findings highlight the nasal susceptibility to SARS-CoV-2 with likely subsequent aspiration-mediated virus seeding to the lung in SARS-CoV-2 pathogenesis. These reagents provide a foundation for investigations into virus-host interactions in protective immunity, host susceptibility, and virus pathogenesis.


Assuntos
Betacoronavirus/genética , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Sistema Respiratório/virologia , Genética Reversa/métodos , Idoso , Animais , Anticorpos Monoclonais/imunologia , Anticorpos Neutralizantes/imunologia , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , Linhagem Celular , Células Cultivadas , Chlorocebus aethiops , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/terapia , Fibrose Cística/patologia , DNA Recombinante , Feminino , Furina/metabolismo , Humanos , Imunização Passiva , Pulmão/metabolismo , Pulmão/patologia , Pulmão/virologia , Masculino , Pessoa de Meia-Idade , Mucosa Nasal/metabolismo , Mucosa Nasal/patologia , Mucosa Nasal/virologia , Pandemias , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/imunologia , Sistema Respiratório/patologia , Serina Endopeptidases/metabolismo , Células Vero , Virulência , Replicação Viral
3.
PLoS One ; 15(6): e0234731, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32544181

RESUMO

Airborne fungi are associated with upper and lower airway inflammatory diseases. Alternaria is commonly found in nasal secretions and induces the production of chemical mediators from sinonasal mucosa. This study aimed to establish an Alternaria-induced chronic rhinosinusitis (CRS) mouse model and determine the influence of host allergic background on the immunopathological characteristics of CRS. BALB/c mice were used for establishing the CRS model. Alternaria was intranasally instilled for 8 or 16 weeks with or without ovalbumin (OVA) presensitization. Total serum IgE and Alternaria-specific IgE levels were measured by enzyme-linked immunosorbent assay (ELISA). Interleukin (IL)-4, IL-10, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α levels in nasal lavage fluid (NLF) and splenocytes were measured by ELISA and their mRNAs and levels of associated transcription factors in sinonasal mucosa were determined with quantitative reverse-transcriptase polymerase chain reaction (RT-PCR). Hematoxylin-eosin staining and periodic acid-Schiff staining were performed to evaluate histological changes. Total serum IgE was increased in both allergic and non-allergic CRS. IL-4 was strongly expressed in NLF in both allergic and non-allergic CRS at 16 weeks and not only eosinophils but also neutrophils were increased in NLF of non-allergic CRS mice. The levels of Th1, Th2, and Treg cytokines and transcription factor mRNAs were significantly increased in sinonasal mucosa of non-allergic CRS mice. Both inflammatory cell infiltration and goblet cell hyperplasia were increased in CRS mice. Repeated intranasal instillation of Alternaria results in sinonasal inflammation with inflammatory cell infiltration. The sinonasal mucosal immune responses against Alternaria were shown to differ depending on the host allergic background.


Assuntos
Alternaria/patogenicidade , Rinite/patologia , Sinusite/patologia , Alternaria/imunologia , Animais , Doença Crônica , Modelos Animais de Doenças , Feminino , Imunoglobulina E/sangue , Interleucina-10/análise , Interleucina-10/genética , Interleucina-10/metabolismo , Interleucina-4/análise , Interleucina-4/genética , Interleucina-4/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Líquido da Lavagem Nasal/química , Mucosa Nasal/metabolismo , Mucosa Nasal/patologia , RNA Mensageiro/metabolismo , Rinite/imunologia , Sinusite/imunologia , Baço/metabolismo , Baço/microbiologia , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Fator de Necrose Tumoral alfa/análise , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
4.
J Laryngol Otol ; 134(4): 332-337, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32238199

RESUMO

OBJECTIVE: To evaluate the colour values of nasal mucosa for the purpose of presenting an objective parameter of allergic rhinitis. METHODS: Seventy-three patients with allergic rhinitis (allergy group) and 73 normal healthy individuals (control group) were included in the study. Endoscopic examinations were conducted, and endoscopic photographs of the septum and both inferior turbinates were taken. The Adobe Photoshop Elements 7.0 software program was used to measure the numerical values of red-green-blue (RGB) colour components in the endoscopic photographs of nasal mucosa. RESULTS: The G and B values were significantly higher in the allergy group compared to the control group (both p < 0.05). Cumulative R, G and B values of all measurement points were significantly higher in the allergy group compared to the control group (p < 0.05). CONCLUSION: Nasal mucosa discolouration can be measured objectively with RGB analysis to aid the diagnosis of allergic rhinitis.


Assuntos
Cor/normas , Endoscopia/métodos , Mucosa Nasal/anatomia & histologia , Fotografação/instrumentação , Rinite Alérgica/diagnóstico , Adulto , Ensaios Clínicos como Assunto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa Nasal/patologia , Septo Nasal/diagnóstico por imagem , Rinite Alérgica/epidemiologia , Rinite Alérgica/patologia , Sensibilidade e Especificidade , Software , Conchas Nasais/diagnóstico por imagem
5.
Artigo em Inglês | MEDLINE | ID: mdl-32233789

RESUMO

Air-liquid interface (ALI) cultures are ex vivo models that are used extensively to study the epithelium of patients with chronic respiratory diseases. However, the in vitro conditions impose a milieu different from that encountered in the patient in vivo, and the degree to which this alters gene expression remains unclear. In this study we employed RNA sequencing to compare the transcriptome of fresh brushings of nasal epithelial cells with that of ALI-cultured epithelial cells from the same patients. We observed a strong correlation between cells cultured at the ALI and cells obtained from the brushed nasal epithelia: 96% of expressed genes showed similar expression profiles, although there was greater similarity between the brushed samples. We observed that while the ALI model provides an excellent representation of the in vivo airway epithelial transcriptome for mechanistic studies, several pathways are affected by the change in milieu.


Assuntos
Mucosa Nasal/metabolismo , Doença Pulmonar Obstrutiva Crônica/genética , Mucosa Respiratória/metabolismo , Transcriptoma , Idoso , Ar , Fumar Cigarros/efeitos adversos , Meios de Cultura/química , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Anotação de Sequência Molecular , Mucosa Nasal/patologia , Cultura Primária de Células , Doença Pulmonar Obstrutiva Crônica/etiologia , Doença Pulmonar Obstrutiva Crônica/metabolismo , Doença Pulmonar Obstrutiva Crônica/patologia , Mucosa Respiratória/patologia , Análise de Sequência de RNA , Conchas Nasais/metabolismo , Conchas Nasais/patologia
6.
Ann Allergy Asthma Immunol ; 124(4): 333-341, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32007569

RESUMO

OBJECTIVE: To review the latest discoveries on airway epithelial cell diversity and remodeling in type 2 inflammation, including nasal polyposis. DATA SOURCES: Reviews and primary research manuscripts were identified from PubMed, Google, and Bioarchives, using the search words airway epithelium, nasal polyposis, or chronic rhinosinusitis with nasal polyposis AND basal cell, ciliated cell, secretory cell, goblet cell, neuroendocrine cell, pulmonary neuroendocrine cell, ionocyte, brush cell, solitary chemosensory cell, microvillus cell, or tuft cell. STUDY SELECTIONS: Studies were selected based on novelty and likely relevance to airway epithelial innate immune functions or the pathobiology of type 2 inflammation. RESULTS: Airway epithelial cells are more diverse than previously appreciated, with specialized subsets, including ionocytes, solitary chemosensory cells, and neuroendocrine cells that contribute to important innate immune functions. In chronic rhinosinusitis with nasal polyposis, the composition of the epithelium is significantly altered. Loss of ciliated cells and submucosal glands and an increase in basal airway epithelial progenitors leads to loss of innate immune functions and an expansion of proinflammatory potential. Type 2 cytokines play a major role in driving this process. CONCLUSION: Airway epithelial remodeling in chronic rhinosinusitis is extensive, leading to loss of innate immune function and enhanced proinflammatory potential. The mechanisms driving airway remodeling and its sequelae deserve further attention before restitution of epithelial differentiation can be considered a reasonable therapeutic target.


Assuntos
Remodelação das Vias Aéreas , Mucosa Nasal/patologia , Pólipos Nasais/patologia , Rinite/patologia , Sinusite/patologia , Doença Crônica , Humanos , Inflamação/imunologia , Inflamação/patologia , Mucosa Nasal/imunologia , Pólipos Nasais/imunologia , Rinite/imunologia , Sinusite/imunologia
7.
Eur J Histochem ; 64(1)2020 01 23.
Artigo em Inglês | MEDLINE | ID: mdl-31988531

RESUMO

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a persistent sinonasal mucosa inflammatory disease with still unclear pathophysiologic mechanisms that imply events of tissue repair and structural remodelling. Several cascades seem to have a considerable role in the onset and progression of mucosa hyperproliferation in nasal polyps including transforming growth factor ß/Small mother against decapentaplegic (TGFß/Smads), mitogenactivated protein kinases (MAPKs), advanced glycosylation end-products (AGEs) together with epithelial-tomesenchymal transition (EMT). Since many inflammatory mediators are reported to play important roles in the development of nasal polyps (NP) disease, this study aimed to analyse the correlation between the AGEs/receptor of advanced glycosylation end-products (RAGE)/extracellular signal-regulated kinase (ERK) signalling pathway and the main markers of EMT to better understand the influence that they exert on the remodelling of nasal mucous membranes in patients affected by CRSwNP vs normal controls. A total of 30 patients were enrolled in this study. Immunohistochemical analysis, using AGE, RAGE, p-ERK, MMP-3, TGF-ß1, Smad2/3, Collagen I-III, α-SMA, E-cadherin, IL-6 and Vimentin antibodies, was performed. AGE, RAGE, ERK, p-ERK and MMP3 were also evaluated using western blot analysis. We observed an overexpression of the AGE/RAGE/p-ERK and the main mesenchymal markers of EMT (Vimentin and IL-6) in CRSwNP vs controls whereas the TGF-ß/Smad3 pathway did not show any significant differences between the two groups of patients. These observations suggest a complex network of processes in the pathogenesis of NP, and the AGE/RAGE/ERK pathway and EMT might work together in promoting tissue remodelling in the formation of CRSwNP.


Assuntos
Transição Epitelial-Mesenquimal/fisiologia , Sistema de Sinalização das MAP Quinases/fisiologia , Pólipos Nasais/etiologia , Sinusite/etiologia , Adulto , Doença Crônica , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Feminino , Produtos Finais de Glicação Avançada/metabolismo , Humanos , Imuno-Histoquímica , Interleucina-6/metabolismo , Masculino , Mucosa Nasal/patologia , Pólipos Nasais/patologia , Pólipos Nasais/fisiopatologia , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Sinusite/patologia , Sinusite/fisiopatologia , Vimentina/metabolismo
8.
Clin Sci (Lond) ; 134(2): 123-138, 2020 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-31922185

RESUMO

Type 2 inflammation and eosinophilic infiltration are prominent pathologic features of chronic rhinosinusitis with nasal polyps (CRSwNP). The purpose of the present study was to determine the roles of Tregs in controlling type 2 inflammation and inhibiting eosinophilic infiltration in CRSwNP. A total of 134 nasal polyps, 67 ostiomeatal complex from chronic rhinosinusitis (CRS) and 62 normal nasal tissues from controls were collected to study the enumeration and function of Tregs cells and the expressions of cytokine profiles via immunofluorescence staining, flow cytometry, qRT-PCR, ELISA, and/or H&E staining. The effects of Tregs on type2 and type3 inflammations were determined in an eosinophilic chronic sinusitis (ECRS) mice model. It was confirmed that the CRSwNP displayed the features of Th2 and Th17 cells-mediated inflammation, accompanying by an increased level of eosinophilic infiltration and the eosinophil cationic protein (ECP), with a decreased frequency of Treg cells. Furthermore, the percentages of CD4+CD25+CD127lowTreg and CD4+CD25+Foxp3+Treg were only decreased in the polyps of CRSwNP but not in the paired peripheral blood. The CRSwNP possessed the decreased Nrp1+Tregs, Helios+Treg, and low TGF-ß and interleukin (IL)-10 expressions in Tregs. The ECRS mice showed similar inflammatory characteristics to CRSwNP patients. The adoptive transfer of CD4+CD25+Foxp3+ Treg cells significantly decreased the inflammatory cytokines, eosinophilic chemotactic factors in the mucosa of the ECRS mice without alteration of the immune balance in the peripheral blood and spleen. In conclusion, CRSwNP showed high type 2 and type3 inflammation and defective Tregs. The induced regulatory T cell (iTreg) may correct the imbalance between immune tolerance and effect via limiting the eosinophil recruitment of mucosa in CRSwNP.


Assuntos
Eosinófilos/imunologia , Inflamação/imunologia , Mucosa Nasal/imunologia , Mucosa Nasal/patologia , Sinusite/imunologia , Linfócitos T Reguladores/imunologia , Adulto , Animais , Grupo com Ancestrais do Continente Asiático , Antígenos CD4/metabolismo , Doença Crônica , Feminino , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Regulação da Expressão Gênica , Humanos , Inflamação/genética , Interleucina-10/biossíntese , Masculino , Camundongos Endogâmicos BALB C , Pólipos Nasais/sangue , Pólipos Nasais/complicações , Pólipos Nasais/genética , Pólipos Nasais/imunologia , Rinite/sangue , Rinite/complicações , Rinite/genética , Rinite/imunologia , Sinusite/sangue , Sinusite/complicações , Sinusite/genética , Células Th17/imunologia , Células Th2/imunologia , Fator de Crescimento Transformador beta/biossíntese
10.
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
16.
Biomed Pharmacother ; 121: 109675, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31810134

RESUMO

OBJECTIVE: Deleted in malignant brain tumors 1 (DMBT1) is a secreted scavenger receptor cysteine-rich (SRCR) protein, predominantly expressed in nasal mucosal epithelial cells. In previous experiments, we found large amounts of DMBT1 present in the nasal cavity mucosa of allergic rhinitis (AR) patients. However, the exact role of DMBT1 in AR remains unclear. This study is to investigate the mechanism through which DMBT1 exerts its effects on AR progression. METHOD: DMBT1 levels in the nasal lavage (NL) fluid and the nasal mucosa in AR and control groups were determined by ELISA and IHC. Next, mice were sensitized with ovalbumin; intranasal administrations of recombinant DMBT1 were then performed. DMBT1 in the nasal mucosa of mice were determined by IHC and WB. Nasal symptoms were estimated. IL-4 and IL-5 in BAL fluid and eosinophils infiltration in the nasal cavity were measured through ELISA and HE staining, respectively. RESULTS: DMBT1 levels were found to be significantly higher in the NL fluid and nasal mucosa of AR patients and AR mice, compared to control groups (p < 0.01). Levels of IL-4 and IL-5 in BAL and infiltration of eosinophils into the nasal mucosa were significantly increased in AR mice, compared to control mice (p < 0.01). rDMBT1 significantly reduced the number of nasal sneezing and rubbings in AR mice (p < 0.01). It also inhibited the eosinophil infiltration in the nasal mucosa and significantly decreased the production of IL-4 and IL-5 in BAL (p < 0.01). CONCLUSION: This study demonstrated that rDMBT1 alleviates AR progression in mice via inhibiting IL-4 and IL-5 production and eosinophils infiltration in the nasal cavity.


Assuntos
Proteínas de Ligação ao Cálcio/metabolismo , Proteínas de Ligação a DNA/metabolismo , Substâncias Protetoras/metabolismo , Rinite Alérgica/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Administração Intranasal , Animais , Líquido da Lavagem Broncoalveolar , Modelos Animais de Doenças , Progressão da Doença , Eosinófilos/metabolismo , Humanos , Imunoglobulina E/sangue , Interleucina-4/metabolismo , Interleucina-5/metabolismo , Modelos Lineares , Masculino , Camundongos Endogâmicos BALB C , Líquido da Lavagem Nasal , Mucosa Nasal/metabolismo , Mucosa Nasal/patologia , Proteínas Recombinantes/farmacologia , Rinite Alérgica/sangue , Rinite Alérgica/patologia , Rinite Alérgica/fisiopatologia , Espirro/efeitos dos fármacos
17.
J Ethnopharmacol ; 248: 112262, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-31585162

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia ordosica Krasch. (AOK) has been used for rheumatic arthritis, cold headache, sore throat, etc. in traditional Chinese/Mongolian medicine and is used for nasosinusitis by local Mongolian "barefoot" doctors. Up to now, their mechanisms are still unclear. AIM: To evaluate the in vivo anti-inflammatory and allergic rhinitis (AR) alleviating effect as well as in vitro antimicrobial activities of AOK extracts to verify its ethno-medicinal claims. MATERIALS AND METHODS: Crude extracts (methanol/95%-ethanol/ethyl acetate) of AOK root/stem/leaf and fractions (petroleum ether/ethyl acetate/n-butanol/aqueous) of AOK root extract were prepared. Xylene-induced ear swelling model in mouse and ovalbumin (OVA)-induced AR model in guinea pig were established. Ear swelling degrees of mice were measured. The numbers of rubbing movement and sneezes of guinea pigs were counted to evaluate the symptoms of AR. The serum levels of histamine, INF-γ, IL-2/4/10, and VCAM-1 were measured by ELISA assay. The histological changes of nasal mucosa were investigated by light microscope after H&E staining. Antimicrobial activities of AOK extracts were also tested. LC-MS/MS analysis was performed to characterize the constituents of active extract and molecular docking was conducted to predict the biological mechanism. RESULTS: In ear-swelling model, extract (100.00 mg/kg) from the ethyl acetate layer of 95% ethanol (100.00 mg/kg) showed better swelling inhibition in mice than positive control (dexamethasone, 191.91 mg/kg). In AR model, extract from the ethyl acetate layer of 95% ethanol significantly alleviated the AR symptoms in guinea pigs, decreased the serum levels of histamine, INF-γ, IL-2/4/10, and VCAM-1, and reduced the infiltration of eosinophil in nasal mucosa. For Staphylococcus aureus, the ethyl acetate extract of AOK stem showed the highest inhibition (MIC=1.25 mg/mL), for Escherichia coli, n-butanol layer of 95% ethanol extract of AOK root showed the highest inhibition (MIC=15.00 mg/mL), for Candida glabrata, 95%-ethyl acetate extract of AOK leaf showed the best inhibition (MIC=0.064 mg/mL), while ethyl acetate and n-butanol layers showed similar inhibition on MRSA (MIC=7.50 mg/mL). LC-MS/MS characterization showed that dicaffeoylquinic acids account for more than 30% of ethyl acetate layer of AOK extract. Dicaffeoylquinic acids bind with histamine-1 receptor with high affinities and interesting modes. CONCLUSIONS: Extracts from AOK had interesting anti-inflammatory activity in mice, alleviating effect against OVA-induced AR in guinea pigs, and antimicrobial activities in vitro, which support the ethno-medicinal use of it. The main constituents in ethyl acetate layer of AOK root extract are dicaffeoylquinic acids and could bind with histamine-1 receptor well. These findings highlighted the importance of natural product chemistry study of AOK.


Assuntos
Antialérgicos/uso terapêutico , Anti-Infecciosos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Artemisia , Extratos Vegetais/uso terapêutico , Rinite Alérgica/tratamento farmacológico , Sinusite/tratamento farmacológico , Alérgenos , Animais , Antialérgicos/farmacologia , Anti-Infecciosos/farmacologia , Anti-Inflamatórios/farmacologia , Candida glabrata/efeitos dos fármacos , Candida glabrata/crescimento & desenvolvimento , Citocinas/imunologia , Edema/induzido quimicamente , Edema/tratamento farmacológico , Escherichia coli/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Cobaias , Masculino , Medicina Tradicional Chinesa , Medicina Tradicional da Mongólia , Camundongos , Simulação de Acoplamento Molecular , Mucosa Nasal/efeitos dos fármacos , Mucosa Nasal/patologia , Ovalbumina , Extratos Vegetais/farmacologia , Receptores Histamínicos H1/metabolismo , Rinite Alérgica/imunologia , Rinite Alérgica/patologia , Sinusite/imunologia , Sinusite/patologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimento , Xilenos
18.
Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi ; 54(11): 850-856, 2019 Nov 07.
Artigo em Chinês | MEDLINE | ID: mdl-31795547

RESUMO

Objective: To explore the expression of amphiregulin (AREG) in nasal polyps patients with different degrees of eosinophil infiltration, and to analyze the correlation between AREG and tissue remodeling. Methods: Forty-eight patients underwent endoscopic sinus surgery in the Department of Otorhinolaryngology Head and Neck Surgery, Remin Hospital, Wuhan University from July 2017 to August 2018 were recruited, including 40 males and 8 females, aged from 16 to 60 years old. The subjects were divided into three groups: control group (n=14), eosinophilic chronic sinusitis with nasal polyps (ECRSwNP) group (n=19) and noneosinophilic chronic rhinosinusitis with nasal polyps (non-ECRSwNP) group (n=15). The relative expression of AREG in nasal mucosa was detected by Western blot assay and immunohistochemical staining. Tissue remodeling was detected by HE staining, AB-PAS staining and Masson staining. Kruskal-Wallis test was used for comparison among multiple groups, and Spearman correlation analysis was conducted between the expression level of AREG and the related indexes of tissue remodeling. Results: The expression of AREG in ECRSwNP group was significantly higher than that in non-ECRSwNP group and control group (median protein expression of Western blot was 1.592 vs 0.617 vs0.582, all P<0.05). The degree of epithelial injury and goblet cell metaplasia in ECRSwNP group was significantly higher than that in control group (all P<0.05), the percentage of collagen fibrosis area in ECRSwNP group was significantly lower than that in control group (P=0.01). In chronic rhinosinusitis with nasal polyps (CRSwNP) patients, the area of mucous glands was negatively correlated with the expression of AREG (r=-0.616, P<0.05), and the percentage of collagen fibrosis area was negatively correlated with the expression of AREG (r=-0.738, P<0.05). Conclusion: The expression of AREG is higher in ECRSwNP patients, which is related to the process of tissue remodeling.


Assuntos
Anfirregulina/biossíntese , Eosinófilos/metabolismo , Mucosa Nasal/metabolismo , Pólipos Nasais/metabolismo , Rinite/metabolismo , Sinusite/metabolismo , Adolescente , Adulto , Doença Crônica , Feminino , Fibrose/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Mucosa Nasal/patologia , Mucosa Nasal/cirurgia , Pólipos Nasais/patologia , Pólipos Nasais/cirurgia , Rinite/patologia , Rinite/cirurgia , Sinusite/patologia , Sinusite/cirurgia , Adulto Jovem
19.
Int J Med Sci ; 16(12): 1631-1641, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31839751

RESUMO

Epithelial-mesenchymal transition (EMT) has been reported to occur in eosinophilic chronic rhinosinusitis with nasal polyps (ECRSwNP). Among the cytokines that cause EMT, high mobility group box 1 (HMGB1) has been shown to give rise to EMT in airway epithelial cells. However, the mechanism of HMGB1-induced EMT in ECRSwNP is unknown. We explored the mechanism and possible inhibitor. Immunohistochemistry (IHC), immunofluorescence (IF), and western blot assay were used to detect the expression and location of HMGB1, peroxisome proliferator-activated receptor-γ (PPAR-γ), and EMT markers in eighteen ECRSwNP and twelve normal nasal mucosa tissues. Epithelial cells isolated from ECRSwNP were cultured with various doses of recombinant human HMGB1 (rhHMGB1) to study the expression of PPAR-γ, and EMT markers. Additionally, the ligand of PPAR-γ was incubated with epithelial cells to interfere with the effects of lipopolysaccharide (LPS) or rhHMGB1 to explore the effect on expression of HMGB1 and EMT markers. These results suggest that HMGB1 was highly expressed in ECRSwNP compared with its expression in control tissues, and EMT was also found highly in ECRSwNP compared with control tissues. Moreover, the cytoplasmic accumulation of HMGB1 in ECRSwNP was obvious compared with normal tissues. We also found dose-dependent induction by rhHMGB1 of up-regulation of N-cadherin and vimentin and down-regulation of ZO-1 and E-cadherin in epithelial cells isolated from ECRSwNP. The agonist of PPAR-γ not only reduced release of HMGB1 induced by LPS, but also reversed the EMT. The protective role of PPAR-γ also appeared in cells that had been incubated with rhHMGB1. In the current study, we discovered that the agonist of PPAR-γ has a potential role in inhibited HMGB1-induced EMT in ECRSwNP. The agonist of PPAR-γ may contribute to inhabit epithelial cells to become mesenchymal-like cells which play an important role in the pathogenesis of ECRSwNP.


Assuntos
Proteína HMGB1/genética , Pólipos Nasais/genética , PPAR gama/genética , Rinite/genética , Sinusite/genética , Caderinas/genética , Células Epiteliais/efeitos dos fármacos , Transição Epitelial-Mesenquimal/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Proteína HMGB1/farmacologia , Humanos , Ligantes , NF-kappa B/genética , Mucosa Nasal/efeitos dos fármacos , Mucosa Nasal/patologia , Pólipos Nasais/complicações , PPAR gama/antagonistas & inibidores , Proteínas Recombinantes/genética , Proteínas Recombinantes/farmacologia , Rinite/complicações , Rinite/patologia , Transdução de Sinais/efeitos dos fármacos , Sinusite/complicações , Sinusite/patologia , Vimentina/genética , Proteína da Zônula de Oclusão-1/genética
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