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Background: /Aims: Epidemiological data show that there is an important relationship between respiratory and intestinal diseases. To improve our understanding on the interconnectedness between the lung and intestinal mucosa and the overlap between respiratory and intestinal diseases, our aim was to investigate the influence of ovalbumin (OVA)-induced allergic airway inflammation on gut homeostasis. Methods: A/J mice were sensitized and challenged with OVA. The animals were euthanized 24 h after the last challenge, lung inflammation was determined by evaluating cells in Bronchoalveolar lavage fluid, serum anti-OVA IgG titers and colon morphology, inflammation and integrity of the intestinal mucosa were investigated. IL-4 and IL-13 levels and myeloperoxidase activity were determined in the colon samples. The expression of genes involved in inflammation and mucin production at the gut mucosa was also evaluated. Results: OVA challenge resulted not only in lung inflammation but also in macroscopic alterations in the gut such as colon shortening, increased myeloperoxidase activity and loss of integrity in the colonic mucosal. Neutral mucin intensity was lower in the OVA group, which was followed by down-regulation of transcription of ATOH1 and up-regulation of TJP1 and MUC2. In addition, the OVA group had higher levels of IL-13 and IL-4 in the colon. Ova-specific IgG1 and OVA-specific IgG2a titers were higher in the serum of the OVA group than in controls. Conclusions: Our data using the OVA experimental model suggested that challenges in the respiratory system may result not only in allergic airway inflammation but also in the loss of gut homeostasis.
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Background Aims: Epidemiological data show that there is an important relationship between respiratory and intestinal diseases. To improve our understanding on the interconnectedness between the lung and intestinal mucosa and the overlap between respiratory and intestinal diseases, our aim was to investigate the influence of ovalbumin (OVA)-induced allergic airway inflammation on gut homeostasis. Methods A/J mice were sensitized and challenged with OVA. The animals were euthanized 24 h after the last challenge, lung inflammation was determined by evaluating cells in Bronchoalveolar lavage fluid, serum anti-OVA IgG titers and colon morphology, inflammation and integrity of the intestinal mucosa were investigated. IL-4 and IL-13 levels and myeloperoxidase activity were determined in the colon samples. The expression of genes involved in inflammation and mucin production at the gut mucosa was also evaluated. Results OVA challenge resulted not only in lung inflammation but also in macroscopic alterations in the gut such as colon shortening, increased myeloperoxidase activity and loss of integrity in the colonic mucosal. Neutral mucin intensity was lower in the OVA group, which was followed by down-regulation of transcription of ATOH1 and up-regulation of TJP1 and MUC2. In addition, the OVA group had higher levels of IL-13 and IL-4 in the colon. Ova-specific IgG1 and OVA-specific IgG2a titers were higher in the serum of the OVA group than in controls. Conclusions Our data using the OVA experimental model suggested that challenges in the respiratory system may result not only in allergic airway inflammation but also in the loss of gut homeostasis.
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INTRODUCTION: Emerging evidence indicates that physiological and pathological conditions of the nose are posttranscriptionally regulated by microRNAs, a class of small noncoding RNAs. Recently, microRNA-223-3p has been increasingly implicated in the modulation of allergic rhinitis OBJECTIVE: This study aimed to assess the role and mechanism of microRNA-223-3p in a mouse model of allergic rhinitis. METHODS: The expression level of miR-223-3p was measured in the serum of 41 allergic rhinitis patients and 39 healthy controls using quantitative real time polymerase chain reaction. BALB/c mice were used to establish an allergic rhinitis model by intraperitoneal sensitization and intranasal challenge with ovalbumin. MicroRNA-223-3p agomir/antagomir was then intranasally administered to mice after ovalbumin challenge for another week. The symptoms of nasal rubbing and sneezing were recorded. Serum ovalbumin-specific immunoglobulin E concentration, microRNA-223-3p expression and proinflammatory cytokine (IL-4, IL-5, IFN-γ) levels in nasal mucosa were measured by ELISA and quantitative real time polymerase chain reaction, respectively. Histopathologic changes were evaluated using hematoxylin and eosin staining. RESULTS: MicroRNA-223-3p levels increased significantly in both allergic rhinitis patients and allergic rhinitis mice. In addition, upregulation of microRNA-223-3p levels by nasal administration of microRNA-223-3p agomir also markedly increased the concentration of ovalbumin -specific IgE, the frequencies of nasal rubbing and sneezing, the levels of proinflammatory cytokines (IL-4, IL-5, IFN-γ) and eosinophil infiltration in the nasal mucosa of allergic rhinitis mice. Moreover, microRNA-223-3p antagomir appeared to strongly ameliorate the symptoms and pathology in nasal mucosa. Subsequently, we demonstrated for the first time that microRNA-223-3p negatively regulated INPP4A expression by binding with the 3' untranslated region (3'UTR) of INPP4A. CONCLUSIONS: These findings indicate that microRNA-223-3p plays an important role in regulating the pathology and symptoms of allergic rhinitis by targeting INPP4A.
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MicroRNAs , Rinite Alérgica , Animais , Citocinas , Modelos Animais de Doenças , Humanos , Inflamação , Camundongos , Camundongos Endogâmicos BALB C , Mucosa NasalRESUMO
Abstract Objective Mold exposure in early life may be associated with development of atopic dermatitis; however, studies of this link are inconclusive and evidence for the underlying mechanism(s) is lacking. This study identified the association between the time of mold exposure and development of atopic dermatitis and investigated the underlying mechanisms. Method The association between atopic dermatitis and mold exposure was examined in the Cohort for Childhood Origin of Asthma and Allergic Diseases birth cohort study (n = 1446). Atopic dermatitis was diagnosed at 1 year of age by pediatric allergists. Exposure to mold was assessed by questionnaire. The Illumina MiSeq platform was used to examine the environmental mycobiome in 20 randomly selected healthy infants and 20 infants with atopic dermatitis at 36 weeks of gestation. Results Prenatal, but not postnatal, mold exposure was significantly associated with atopic dermatitis (adjusted odds ratio, 1.36; 95% confidence interval, 1.01-1.83). Levels of total serum IgE at 1 year of age were higher in infants with atopic dermatitis exposed to mold during pregnancy than in healthy infants not exposed to mold during pregnancy (p = 0.021). The relative abundance of uncultured Ascomycota was higher in infants with atopic dermatitis than in healthy infants. The relative abundance of uncultured Ascomycota correlated with total serum IgE levels at 1 year of age (r = 0.613, p < 0.001). Conclusion Indoor mold exposure during the fetal period is associated with development of atopic dermatitis via IgE-mediated allergic inflammation. Avoidance of mold exposure during this critical period might prevent the development of atopic dermatitis.
Resumo Objetivo A exposição ao mofo no início da vida pode estar associada ao desenvolvimento de dermatite atópica; contudo, os estudos sobre esse vínculo são inconclusivos e faltam evidências dos mecanismos subjacentes. Identificamos a associação entre o momento da exposição ao mofo e o desenvolvimento de dermatite atópica e investigamos os mecanismos subjacentes. Método A associação entre dermatite atópica e exposição a mofo foi examinada em um estudo de coorte de nascimento da Origem da Asma e de Doenças Alérgicas em Crianças (COCOA) (n = 1446). A dermatite atópica foi diagnosticada em pacientes com um ano de vida por pediatras alergistas. A exposição ao mofo foi avaliada por um questionário. A plataforma Illumina MiSeq foi utilizada para examinar o microbioma ambiental em 20 neonatos saudáveis escolhidos aleatoriamente e 20 com dermatite atópica a 36 semanas de gestação. Resultados A exposição pré-natal, porém não pós-natal, ao mofo foi significativamente associada à dermatite atópica (razão de chances ajustada, 1,36; intervalo de confiança de 95%, 1,01-1,83). Os níveis séricos totais de Imunoglobulina E (IgE) no primeiro ano de vida foram maiores em neonatos com dermatite atópica expostos a mofo durante a gravidez do que em neonatos não expostos a mofo durante a gravidez (p = 0,021). A abundância relativa de Ascomycota não cultivado foi maior em neonatos com dermatite atópica do que em neonatos saudáveis. A abundância relativa de Ascomycota não cultivado correlacionou-se com os níveis séricos totais de IgE no primeiro ano de vida (r = 0,613, p < 0,001). Conclusão A exposição ao mofo no ambiente domiciliar durante a gravidez está associada ao desenvolvimento de dermatite atópica por meio de reação alérgica mediada por IgE. A prevenção à exposição ao mofo durante o período crítico da gravidez pode prevenir o desenvolvimento de dermatite atópica.
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Humanos , Feminino , Gravidez , Lactente , Criança , Asma , Dermatite Atópica/etiologia , Inflamação/etiologia , Razão de Chances , Estudos de Coortes , FungosRESUMO
OBJECTIVE: Mold exposure in early life may be associated with development of atopic dermatitis; however, studies of this link are inconclusive and evidence for the underlying mechanism(s) is lacking. This study identified the association between the time of mold exposure and development of atopic dermatitis and investigated the underlying mechanisms. METHOD: The association between atopic dermatitis and mold exposure was examined in the Cohort for Childhood Origin of Asthma and Allergic Diseases birth cohort study (n=1446). Atopic dermatitis was diagnosed at 1 year of age by pediatric allergists. Exposure to mold was assessed by questionnaire. The Illumina MiSeq platform was used to examine the environmental mycobiome in 20 randomly selected healthy infants and 20 infants with atopic dermatitis at 36 weeks of gestation. RESULTS: Prenatal, but not postnatal, mold exposure was significantly associated with atopic dermatitis (adjusted odds ratio, 1.36; 95% confidence interval, 1.01-1.83). Levels of total serum IgE at 1 year of age were higher in infants with atopic dermatitis exposed to mold during pregnancy than in healthy infants not exposed to mold during pregnancy (p=0.021). The relative abundance of uncultured Ascomycota was higher in infants with atopic dermatitis than in healthy infants. The relative abundance of uncultured Ascomycota correlated with total serum IgE levels at 1 year of age (r=0.613, p<0.001). CONCLUSION: Indoor mold exposure during the fetal period is associated with development of atopic dermatitis via IgE-mediated allergic inflammation. Avoidance of mold exposure during this critical period might prevent the development of atopic dermatitis.
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Asma , Dermatite Atópica , Inflamação/etiologia , Criança , Estudos de Coortes , Dermatite Atópica/etiologia , Feminino , Fungos , Humanos , Lactente , Razão de Chances , GravidezRESUMO
Combined allergic rhinitis and asthma syndrome (CARAS) is a concept of "one airway - one disease" or "unified airway disease ". The upper and lower airway inflammation characterizes allergic rhinitis and asthma, respectively and both diseases have shown an intimate connection in their genesis, coexistence and similarities as triggered by the same etiological agents; the same inflammatory cell profile and share therapeutic treatment. This review highlights the concept of CARAS by its phenotype, endotype and biomarker classification. Indeed, rhinitis is divided into four major phenotypes: allergic rhinitis; infectious rhinitis; non-infective/non-allergic rhinitis and mixed rhinitis. On the other hand, asthma has no common consensus yet; however, the most accepted classification is based on the stage of life (early- or late- onset asthma) in which the clinical symptoms are presented. Experimental researches where animals develop a syndrome similar to CARAS have been contributed to better understand the pathogenesis of the syndrome. Therefore, the aim of this review is to clarify current terms related to CARAS as definition, phenotypes, endotypes/biomarkers, physiopathology and treatments.
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Asma , Sistema Respiratório/imunologia , Rinite Alérgica , Animais , Biomarcadores , Modelos Animais de Doenças , Humanos , Inflamação , Fenótipo , SíndromeRESUMO
Allergic inflammation is a response of the body against pathogens by cytokine release and leucocyte recruitment. Recently, there was an increase in morbimortality associated with allergic inflammation, especially asthma. The treatment has many adverse effects, requiring the search for new therapies. Monoterpenes are natural products with anti-inflammatory activity demonstrated in several studies and can be an option to inflammation management. Thus, we investigated the effects of citronellol, α-terpineol and carvacrol on allergic inflammation. The model of asthma was established by OVA induction in male Swiss mice. The monoterpenes were administered (25, 50 or 100 mg/kg, i.p.) 1 h before induction. After 24hs, the animals were sacrificed to leucocytes and TNF-α quantification. Monoterpenes significantly decrease leucocyte migration and TNF-α levels, possibly by modulation of COX, PGE2 and H1 receptor, as demonstrated by molecular docking. These findings indicate that alcoholic monoterpenes can be an alternative for treatment of allergic inflammation and asthma.
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Citocinas/metabolismo , Inflamação/tratamento farmacológico , Monoterpenos/farmacologia , Óleos Voláteis/química , Especiarias , Animais , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , Asma/induzido quimicamente , Asma/tratamento farmacológico , Inibidores de Ciclo-Oxigenase 2/química , Inibidores de Ciclo-Oxigenase 2/farmacologia , Dinoprostona/metabolismo , Modelos Animais de Doenças , Inflamação/induzido quimicamente , Masculino , Camundongos , Simulação de Acoplamento Molecular , Monoterpenos/química , Ovalbumina/efeitos adversos , Receptores Histamínicos H1/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
MHTP [2-methoxy-4-(7-methoxy-1,2,3,4-tetrahydroisoquinolin-1-yl) phenol], a synthetic isoquinolinic alkaloid, presented anti-inflammatory activity in several experimental models of acute inflammation as lipopolysaccharide (LPS)-induced acute lung injury and phlogistic agent-induced edema and presented low preclinical toxicity. The aim of this study was to determine the MHTP effect on ovalbumin (OVA)-induced pulmonary allergic inflammation. In other to realize this study, female BALFB/c mice were sensitized and challenged with OVA (OVA group) and treated with MHTP (MHTP group) by nasal instillation. Inflammatory, allergic, and immunomodulatory parameters such as migration of inflammatory cells to the lung tissue, pulmonary histological analysis, serum level of IgE-allergen specific, cytokine secretion, and lung T cell population characterization were analyzed and the data were considered statistically significant with p < 0.05. OVA-sensitized and OVA-challenged and MHTP (5.0 mg/kg)-treated mice presented reduction on total leukocyte migration into the bronchoalveolar lavage (BALF) dependent of lymphocyte and eosinophil migration (p < 0.001 and p < 0.01) as compared with the OVA group. Flow cytometric analysis showed that MHTP treatment decreased the percentage of granulocytes (p < 0.001) into the BALF and lung tissue histological analyzes demonstrated that the MHTP treatment decreased leukocyte migration and mucus production. In addition, treatment with MHTP decreased the number of CD3+CD4+ T cells independently of CD8+ T cell reduction into the BALF. The treatment also reduced significantly (p < 0.05) the serum level of IgE-OVA specific followed by reduction of IL-4, IL-13, and IL-17 production. Surprisingly, the MHTP treatment increased significantly (p < 0.05) the IFN-γ production in the BALF of these animals. Therefore, the results presented here showed that MHTP treatment, by nasal instillation, in a mouse model of OVA-induced pulmonary allergy has anti-allergic and immunomodulatory effects dependent on a Th1-skewed cytokine production that ameliorate the pulmonary allergic inflammation.
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Asma/metabolismo , Interferon gama/biossíntese , Tetra-Hidroisoquinolinas/farmacologia , Animais , Asma/tratamento farmacológico , Asma/patologia , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Citocinas/efeitos dos fármacos , Feminino , Granulócitos/citologia , Granulócitos/efeitos dos fármacos , Inflamação/tratamento farmacológico , Interferon gama/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Ovalbumina , Linfócitos T/citologia , Linfócitos T/efeitos dos fármacos , Células Th1/imunologiaRESUMO
Asthma is an allergic inflammation driven by the Th2 immune response with release of cytokines such as IL-4 and IL-13, which contribute to the airflow limitations and airway hyperresponsiveness (AHR). The involvement of oxidative stress in this process is well-established, but the specific role of the superoxide anion and nitric oxide in asthma are poorly understood. Thus, the aim of this study was to investigate the mechanisms underlying the superoxide anion/nitric oxide production and detoxification in a murine asthma model. BALB/c male mice were sensitised and challenged with ovalbumin (OVA). Pretreatments with either apocynin (14 mg/kg) or allopurinol (25 mg/kg) (superoxide anion synthesis inhibitors), aminoguanidine (50 mg/kg) (nitric oxide synthesis inhibitor) or diethyldithiocarbamate (100 mg/kg) (superoxide dismutase inhibitor) were performed 1 h before the challenge. Our data showed that apocynin and allopurinol ameliorated AHR and reduced eosinophil peroxidase, as well as IL-4 and IL-13 levels. Apocynin also abrogated leukocyte peribronchiolar infiltrate and increased IL-1ß secretion. Aminoguanidine preserved lung function and shifted the Th2 to the Th1 response with a reduction of IL-4 and IL-13 and increase in IL-1ß production. Diethyldithiocarbamate prevented neither allergen-induced AHR nor eosinophil peroxidase (EPO) generation. All treatments protected against oxidative damage observed by a reduction in TBARS levels. Taken together, these results suggest that AHR in an asthma model can be avoided by the down-regulation of superoxide anion and nitric oxide synthesis in a mechanism that is independent of a redox response. This down-regulation is also associated with a transition in the typical immunological Th2 response toward the Th1 profile.
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Asma/imunologia , Inflamação/imunologia , Óxido Nítrico/antagonistas & inibidores , Hipersensibilidade Respiratória/imunologia , Superóxidos/antagonistas & inibidores , Acetofenonas/administração & dosagem , Alopurinol/administração & dosagem , Animais , Asma/metabolismo , Asma/patologia , Modelos Animais de Doenças , Peroxidase de Eosinófilo/imunologia , Peroxidase de Eosinófilo/metabolismo , Guanidinas/administração & dosagem , Humanos , Hipersensibilidade/imunologia , Hipersensibilidade/metabolismo , Hipersensibilidade/patologia , Inflamação/metabolismo , Inflamação/patologia , Interleucina-13/imunologia , Interleucina-13/metabolismo , Interleucina-1beta/imunologia , Interleucina-1beta/metabolismo , Interleucina-4/imunologia , Interleucina-4/metabolismo , Camundongos , Óxido Nítrico/imunologia , Ovalbumina/imunologia , Estresse Oxidativo/imunologia , Espécies Reativas de Oxigênio/imunologia , Espécies Reativas de Oxigênio/metabolismo , Hipersensibilidade Respiratória/metabolismo , Hipersensibilidade Respiratória/patologia , Superóxidos/imunologia , Células Th1/imunologia , Células Th2/imunologiaRESUMO
Lungs are indispensable organs for the respiratory process, and maintaining their homeostasis is essential for human health and survival. However, during the lifetime of an individual, the lungs suffer countless insults that put at risk their delicate organization and function. Many cells of the immune system participate to maintain this equilibrium and to keep functional lungs. Among these cells, mast cells have recently attracted attention because of their ability to rapidly secrete many chemical and biological mediators that modulate different processes like inflammation, angiogenesis, cell proliferation, etc. In this review, we focus on recent advances in the understanding of the role that mast cells play in lung protection during infections, and of the relation of mast cell responses to type I hypersensitivity-associated pathologies. Furthermore, we discuss the potential role of mast cells during wound healing in the lung and its association with lung cancer, and how mast cells could be exploited as therapeutic targets in some diseases.
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AIMS: Stress mechanisms paradoxically contribute to allergic episodes in humans and mice. Glucocorticoids (GC) and interleukin (IL)-5 synergically upregulate murine bone-marrow eosinophil production. Here we explored the role of endogenous GC in allergen-stimulated bone-marrow eosinophil production in ovalbumin-sensitized/challenged mice. MAIN METHODS: In BALB/c or C57BL/6 mice, sensitized and intranasally challenged with ovalbumin, we monitored eosinophil numbers in freshly harvested or cultured bone-marrow, and plasma corticosterone levels. Metyrapone (MET) was used to inhibit GC synthesis, and RU486 to block GC actions. In sensitized mice challenged intraperitoneally, we examined the relationship between eosinophilia of bone-marrow and peritoneal cavity, in the absence or presence of RU486. In experiments involving in vivo neutralization of tumor necrosis factor-α (TNF) by specific antibodies, or using mice which lack functional type I TNF receptors (TNFRI), we evaluated the relationship between TNF blockade, corticosterone levels, RU486 or MET treatment and challenge-induced bone-marrow eosinophilia. KEY FINDINGS: RU486 or MET pretreatments abolished challenge-induced increases in eosinophil numbers in bone-marrow (in vivo and ex vivo), and in the peritoneal cavity. MET, but not RU486, prevented the challenge-induced increase in corticosterone levels. Challenge-induced bone-marrow eosinophilia and corticosterone surge were abolished in TNFRI-deficient mice. Anti-TNF-treatment very effectively prevented challenge-induced bone-marrow eosinophilia, in the absence of RU486 or MET, but had no independent effect in the presence of either drug. SIGNIFICANCE: Endogenous GC was essential for allergen challenge-induced increases in eosinophil numbers inside bone-marrow. This effect required TNF and TNFRI, which suggests an immunoendocrine mechanism.
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Eosinofilia/metabolismo , Eosinófilos/metabolismo , Glucocorticoides/metabolismo , Receptores Tipo I de Fatores de Necrose Tumoral/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Animais , Medula Óssea/metabolismo , Corticosterona/metabolismo , Feminino , Glucocorticoides/biossíntese , Inflamação/fisiopatologia , Metirapona/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Mifepristona/farmacologia , Ovalbumina/imunologia , Cavidade PeritonealRESUMO
Introducción. El asma alérgica es una de las enfermedades más prevalecientes en la edad pediátrica. Los mecanismos implicados en este padecimiento no han sido esclarecidos totalmente. Se sabe que el factor de crecimiento transformante-beta (TGF-β) juega un papel muy importante en la fisiopatología de esta enfermedad y que la activación del factor de trascripción Yin-Yang-1 (YY1) induce un aumento en la expresión de esta citocina. El factor YY1 también regula la expresión de otras citocinas involucradas en el asma tales como la IL-4 y la IL-10. El objetivo de este trabajo fue evaluarla asociación entre YY1 y TGF-β en un modelo murino de inflamación alérgica pulmonar. Métodos. Se trabajó con un modelo murino de inflamación alérgica pulmonar con diferentes grados de severidad empleando ovalbúmina como alérgeno. Posteriormente se obtuvo el tejido pulmonar, que fue incluido en parafina, se construyó un microarreglo del tejido en un equipo semiautomático y, mediante inmunohistoquímica, se evaluó la expresión de YY1 y de TGF-β La densidad de la expresión se midió de manera cuantitativa por métodos computarizados. Resultados. Se observó inflamación alérgica pulmonar diferencial acorde con el grado de severidad del modelo; se observó el mismo patrón con la producción de moco. La expresión de ambas proteínas se correlacionó de manera directa con el grado de severidad de la inflamación alérgica pulmonar. Conclusiones. Los resultados obtenidos corroboran el papel que juegan ambas proteínas en la fisiopatología de la inflamación alérgica pulmonar.
Background. Allergic asthma is one of the most prevalent childhood diseases. This disease is characterized by airway inflammation and remodelling. The mechanisms implicated in the pathogenesis of this disease remain unclear. Several studies have shown that TGF-β plays an important role in the pathogenesis of asthma. In addition, the polymorphism of the TGF-β promoter region results in the overexpression of TGF-β via regulation of the transcription factor Yin-Yang-1 (YY1). It is has recently been demonstrated that YY1 may be involved in the pathogenesis of asthma by the regulation of IL-4 and IL-10. The aim of this study was to evaluate the association between the YY1 and TGF-β expression levels in a murine model of lung allergic inflammation. Methods. In this study we used a lung allergic inflammatory murine model with different severity degrees. Tissue microarray technology and immunohistochemistry were used to evaluate YY1 and TGF-p expression. The density expression was measured by quantitative methods using specific software. Results. Expression of both proteins correlated with the degrees of severity of lung allergic inflammation. A similar result was observed with mucus production. Conclusions. These results corroborate the role of YY1 and TGF-p in the pathogenesis of this disease.
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Durante la última década se han descubierto tres péptidos con actividad quimotáctica específica para los eosinófilos y que son miembros de la familia de las quimocinas. Estas citocinas inducen a los eosinófilos a realizar diferentes funciones como quimotaxis, migración transendotelial e inducción de la liberación de radicales de oxígeno. Como los eosinófilos infiltran tanto las vías aéreas de pacientes asmáticos como los pólipos nasales, se ha postulado que las eotaxinas pueden ser responsables del reclutamiento de estas células. Los eosinófilos tienen la propiedad de inducir remodelamiento de la matriz extracelular y daño tisular a través de la liberación de proteasas tóxicas, mediadores inflamatorios, citocinas y radicales de oxígeno. Por lo cual, el desarrollo de estrategias terapéuticas que inhiban el reclutamiento de estas células constituye una esperanza en el tratamiento de las enfermedades alérgicas. Este artículo revisa la función de las eotaxinas en asma y poliposis nasal, además de discutir el posible uso de antagonistas de CCR3, receptor de las eotaxinas, como una nueva modalidad terapéutica de asma y poliposis nasal.
Over the last few years, three specific eosinophil activating peptides, eotaxin-1, -2 and -3, members of the chemokine family have been identified. These cytokines exert a number of functions on eosinophils including chemotaxis, transendothelial migration and induction of the release of reactive oxygen species. Eosinophils are considered to play an important role in allergic disease by causing tissue damage through the release of toxic proteases, lipid mediators, cytokines and oxygen free radicals. This article reviews the role of eotaxins in asthma and nasal polyps. Discussion focuses on therapeutic guidelines, particularly as it has been shown that CCR3, the major chemokine receptor in eosinophils, serves as a eotaxin receptor.