Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 60
Filtrar
Más filtros

Base de datos
País/Región como asunto
Tipo del documento
Intervalo de año de publicación
1.
Respir Investig ; 62(4): 695-701, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38815413

RESUMEN

BACKGROUND: Because exacerbation of severe asthma decreases patients' quality of life, this study aimed to identify predictive factors for asthma exacerbation. METHODS: Japanese patients with severe asthma requiring treatment according to the Global Initiative for Asthma (GINA) guidelines ≥ Step 4 between January 2018 and August 2021 were prospectively enrolled and followed up for one year at facilities participating in the Okayama Respiratory Disease Study Group (Okayama Severe Asthma Research Program). RESULTS: A total of 85 patients (29 men and 56 women) were included. The median age was 64 (interquartile range [IQR], 51-72) years. Treatment according to GINA Steps 4 and 5 was required in 29 and 56 patients, respectively, and 44 patients (51.8%) were treated with biologics. The median peripheral-blood eosinophil count, fractional exhaled nitric oxide, IgE level, and percent predicted FEV1 (%FEV1) at enrollment were 204 (IQR, 49-436)/µL, 28 (IQR, 15-43) ppb, 172 (IQR, 56-473) IU/mL, and 80.0 (IQR, 61.1-96.1) %, respectively. Exacerbation during the previous year, asthma control test (ACT) score <20, %FEV1 <60%, and serum IL-10 level >6.7 pg/mL were associated with exacerbation during the observation period. CONCLUSIONS: Exacerbation during the previous year, low ACT score, and low %FEV1 were predictive factors of future exacerbation, even in a cohort with >50% of patients treated with biologics. Furthermore, high serum IL-10 levels might be a new predictive factor.


Asunto(s)
Asma , Progresión de la Enfermedad , Índice de Severidad de la Enfermedad , Humanos , Asma/tratamiento farmacológico , Masculino , Femenino , Persona de Mediana Edad , Anciano , Inmunoglobulina E/sangre , Interleucina-10/sangre , Eosinófilos , Estudios de Cohortes , Estudios Prospectivos , Japón , Volumen Espiratorio Forzado , Pueblos del Este de Asia
2.
Acta Med Okayama ; 77(6): 671-674, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38145943

RESUMEN

A 74-year-old Japanese woman presented with a 45-year history of refractory asthma. She had been treated with inhaled corticosteroids, a long-acting ß2-agonist, and a long-acting muscarinic antagonist for 6 months. She also had a repeated viral infection. Her condition had been characterized as a refractory asthma associated with type 2 and non-type 2 traits. We began treatment with tezepelumab. The control of the patient's asthma symptoms and quality of life improved greatly within 1 month (changes in eosinophil count from 748 to 96 /µL, in FeNO from 32 to 17 ppb, in the Asthma Quality of Life Questionnaire score from 3.59 to 6.68, and in the Asthma Control Test score from 13 to 23). Tezepelumab was effective as an initial biologic agent for a patient with refractory asthma associated with type 2 and non-type 2 traits.


Asunto(s)
Antiasmáticos , Asma , Productos Biológicos , Humanos , Femenino , Anciano , Antiasmáticos/uso terapéutico , Calidad de Vida , Asma/complicaciones , Asma/tratamiento farmacológico , Productos Biológicos/uso terapéutico
3.
Arerugi ; 71(9): 1082-1090, 2022.
Artículo en Japonés | MEDLINE | ID: mdl-36372417
4.
Thorac Cancer ; 13(11): 1735-1738, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35545933

RESUMEN

Here, we report a case of a pulmonary invasive mucinous adenocarcinoma harboring KRAS G12D, diagnosed from tumor samples containing a very small amount of tumor cells using next-generation sequencing (NGS) and the recently developed Lung Cancer Compact Panel. A 79-year-old woman without any respiratory symptoms underwent chest computed tomography, which revealed a tumor in the left lower lobe. During endobronchial ultrasound (EBUS)-guided transbronchial biopsy (TBB) using a guide sheath (GS), a sufficient specimen for pathological diagnosis could not be obtained because the patient had a severe cough and pulmonary bullae located adjacent to the tumor. In the absence of EBUS transbronchial biopsy findings using a guide sheath, brush cytology was used to categorize the tumor as class II (Papanicolaou classification). However, the wash fluid from the cytological examination contained enough cells to obtain sufficient nucleic acid for use in sequencing analysis. The latter revealed KRAS G12D expression. Although the patient underwent surgery without pathological evidence, the evaluation of the surgical specimen confirmed a diagnosis of pulmonary invasive mucinous adenocarcinoma. Use of the Lung Cancer Compact Panel enabled the detection of KRAS G12D in the wash fluid of a brush cytology sample and thus a diagnosis of pulmonary invasive mucinous adenocarcinoma.


Asunto(s)
Adenocarcinoma del Pulmón , Adenocarcinoma Mucinoso , Neoplasias Pulmonares , Adenocarcinoma del Pulmón/genética , Adenocarcinoma Mucinoso/diagnóstico , Adenocarcinoma Mucinoso/genética , Adenocarcinoma Mucinoso/cirugía , Anciano , Broncoscopía/métodos , Femenino , Humanos , Biopsia Guiada por Imagen/métodos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/cirugía , Proteínas Proto-Oncogénicas p21(ras)/genética
5.
Am J Physiol Lung Cell Mol Physiol ; 321(5): L925-L940, 2021 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-34524907

RESUMEN

Acute exacerbation of idiopathic pulmonary fibrosis has a poor prognosis associated with neutrophilic inflammation. Interleukin-23 is a proinflammatory cytokine involved in neutrophilic inflammation. However, little is known about its role in acute exacerbation of pulmonary fibrosis. This study was performed to determine the role of interleukin-23 in acute exacerbation of pulmonary fibrosis. For assessment of acute exacerbation of pulmonary fibrosis, mice were intratracheally administered bleomycin followed by lipopolysaccharide. Inflammatory cells, cytokine levels, and morphological morphometry of the lungs were analyzed. Cytokine levels were measured in the bronchoalveolar lavage fluid of idiopathic pulmonary fibrosis patients with or without acute exacerbation. Interleukin-23, -17A, and -22 levels were increased in the airway of mice with acute exacerbation of pulmonary fibrosis. Interleukin-23p19-deficient mice with acute exacerbation of pulmonary fibrosis had markedly reduced airway inflammation and fibrosis associated with decreased levels of interleukin-17A and -22 compared with wild-type mice. Treatment with an anti-interleukin-23 antibody attenuated airway inflammation and fibrosis and reduced interleukin-17A and -22 levels in mice with acute exacerbation of pulmonary fibrosis. T-helper type 17 cells were the predominant source of interleukin-17A in mice with acute exacerbation of pulmonary fibrosis. Interleukin-23 levels in bronchoalveolar lavage fluid tended to be higher in idiopathic pulmonary fibrosis patients with than without acute exacerbation. The data presented here suggest that interleukin-23 is essential for the development of acute exacerbation of pulmonary fibrosis and that blockade of interleukin-23 may be a new therapeutic strategy for acute exacerbation of pulmonary fibrosis.


Asunto(s)
Fibrosis Pulmonar Idiopática/etiología , Fibrosis Pulmonar Idiopática/inmunología , Inflamación/metabolismo , Interleucina-23/metabolismo , Enfermedad Aguda , Animales , Fibrosis Pulmonar Idiopática/metabolismo , Inflamación/patología , Interleucina-17/inmunología , Interleucina-17/metabolismo , Interleucina-23/inmunología , Interleucinas/inmunología , Interleucinas/metabolismo , Pulmón/inmunología , Pulmón/patología , Ratones , Células Th17/inmunología , Células Th17/metabolismo
6.
Respir Res ; 22(1): 150, 2021 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-33992109

RESUMEN

BACKGROUND: IL-33, which is known to induce type 2 immune responses via group 2 innate lymphoid cells, has been reported to contribute to neutrophilic airway inflammation in chronic obstructive pulmonary disease. However, its role in the pathogenesis of emphysema remains unclear. METHODS: We determined the role of interleukin (IL)-33 in the development of emphysema using porcine pancreas elastase (PPE) and cigarette smoke extract (CSE) in mice. First, IL-33-/- mice and wild-type (WT) mice were given PPE intratracheally. The numbers of inflammatory cells, and the levels of cytokines and chemokines in the bronchoalveolar lavage (BAL) fluid and lung homogenates, were analyzed; quantitative morphometry of lung sections was also performed. Second, mice received CSE by intratracheal instillation. Quantitative morphometry of lung sections was then performed again. RESULTS: Intratracheal instillation of PPE induced emphysematous changes and increased IL-33 levels in the lungs. Compared to WT mice, IL-33-/- mice showed significantly greater PPE-induced emphysematous changes. No differences were observed between IL-33-/- and WT mice in the numbers of macrophages or neutrophils in BAL fluid. The levels of hepatocyte growth factor were lower in the BAL fluid of PPE-treated IL-33-/- mice than WT mice. IL-33-/- mice also showed significantly greater emphysematous changes in the lungs, compared to WT mice, following intratracheal instillation of CSE. CONCLUSION: These observations suggest that loss of IL-33 promotes the development of emphysema and may be potentially harmful to patients with COPD.


Asunto(s)
Interleucina-33/deficiencia , Pulmón/metabolismo , Elastasa Pancreática , Neumonía/metabolismo , Enfisema Pulmonar/metabolismo , Humo , Productos de Tabaco , Animales , Líquido del Lavado Bronquioalveolar/química , Modelos Animales de Enfermedad , Femenino , Factor de Crecimiento de Hepatocito/metabolismo , Proteína Antagonista del Receptor de Interleucina 1/metabolismo , Interleucina-33/genética , Pulmón/patología , Ratones Endogámicos C57BL , Ratones Noqueados , Neumonía/etiología , Neumonía/genética , Neumonía/patología , Enfisema Pulmonar/etiología , Enfisema Pulmonar/genética , Enfisema Pulmonar/patología
7.
PLoS One ; 15(8): e0236935, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32853277

RESUMEN

BACKGROUND: Nintedanib is a multi-kinase inhibitor approved for idiopathic pulmonary fibrosis (IPF); however, its efficacy and safety for patients with IPF and restricted pulmonary function remain unclear. Therefore, the objective of this study was to determine the efficacy and safety of nintedanib for patients with IPF and forced vital capacity (FVC) ≤ 50%. METHODS: This was a multi-center retrospective study performed by the Okayama Respiratory Disease Study Group. Patients were allocated into FVC ≤ 50% and FVC > 50% groups based on their predicted FVC. The primary endpoints were FVC changes from baseline after 6 and 12 months. RESULTS: 45 patients were eligible for the study. 18 patients had FVC ≤ 50%, and 27 patients had FVC > 50%. Overall, 31 and 19 patients underwent pulmonary function tests at 6 and 12 months after initiating nintedanib, respectively. FVC changes from baseline at 6 and 12 months after initiating nintedanib were comparable between the two groups. Adverse events were seen in all patients, and the rates of patients who discontinued nintedanib were also comparable (38.9% vs. 37.0%, p = 1.000). Multiple regression analysis showed that age and forced expiratory volume in 1 second (FEV1)/FVC were negatively correlated with changes in FVC at 6 months after initiating nintedanib. CONCLUSIONS: Our data suggest that nintedanib can be a useful agent for IPF patients, including those with a low FVC, and that age and FEV1/FVC are predictive markers for changes in FVC following nintedanib treatment.


Asunto(s)
Fibrosis Pulmonar Idiopática/tratamiento farmacológico , Fibrosis Pulmonar Idiopática/fisiopatología , Indoles/uso terapéutico , Seguridad , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Indoles/efectos adversos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Capacidad Vital
8.
Respir Investig ; 58(3): 185-189, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32102769

RESUMEN

BACKGROUND: Pirfenidone suppresses the decline of forced vital capacity (FVC) in patients with idiopathic pulmonary fibrosis (IPF). However, IPF progresses in some patients despite treatment. We analyzed patients with meaningful FVC declines during pirfenidone treatment and explored the factors predictive of disease progression after FVC decline. METHODS: This study was a retrospective, multicenter, observational study conducted by the Okayama Respiratory Disease Study Group. We defined initial decline in %FVC as 5% or greater per 6-month period during pirfenidone treatment. IPF patients who were treated with pirfenidone and experienced an initial decline from December 2008 to September 2017 were enrolled. RESULTS: We analyzed 21 patients with IPF. After the initial decline, 4 (19.0%) patients showed improvement in disease, 11 (52.4%) showed stable disease, and 6 (28.6%) showed progressive disease. There was no significant correlation between %FVC reduction on initial decline and subsequent %FVC change (p = 0.475). Deterioration of high-resolution computed tomography (HRCT) findings on initial decline was observed significantly more often in the progressive versus improved/stable disease groups (100% vs 20.0%, p = 0.009). CONCLUSIONS: We revealed that deterioration of HRCT findings may predict disease progression after the initial decline in %FVC in IPF patients treated with pirfenidone.


Asunto(s)
Progresión de la Enfermedad , Fibrosis Pulmonar Idiopática/diagnóstico por imagen , Fibrosis Pulmonar Idiopática/tratamiento farmacológico , Piridonas/uso terapéutico , Intensificación de Imagen Radiográfica/métodos , Tomografía Computarizada por Rayos X/métodos , Capacidad Vital , Humanos , Fibrosis Pulmonar Idiopática/fisiopatología , Valor Predictivo de las Pruebas , Estudios Retrospectivos
9.
Respir Res ; 20(1): 2, 2019 Jan 03.
Artículo en Inglés | MEDLINE | ID: mdl-30606200

RESUMEN

BACKGROUND: Retinoid X receptors (RXRs) are members of the nuclear receptor (NR) superfamily that mediate signalling by 9-cis retinoic acid, a vitamin A derivative. RXRs play key roles not only as homodimers but also as heterodimeric partners, e.g., for retinoic acid receptors, vitamin D receptors, and peroxisome proliferator-activated receptors. The NR family may also play important roles in the development of emphysema. However, the role of RXRs in the pathogenesis of emphysema is not well defined. METHODS: We developed a novel RXR partial agonist (NEt-4IB) and investigated its effect and mechanism compared to a full agonist (bexarotene) in a murine model of emphysema. For emphysema induction, BALB/c mice received intraperitoneal cigarette smoke extract (CSE) or intratracheal porcine pancreas elastase (PPE). Treatment with RXR agonists was initiated before or after emphysema induction. RESULTS: Treatment with NEt-4IB significantly suppressed the increase in static lung compliance and emphysematous changes in CSE-induced emphysema and PPE-induced established and progressive emphysema. NEt-4IB significantly suppressed PPE-induced neutrophilic airway inflammation and the levels of keratinocyte chemoattractant (KC), C-X-C motif ligand5 (CXCL5), interferon (IFN)-γ and IL-17. NEt-4IB also improved the matrix metalloproteinase-9 (MMP-9)/tissue inhibitor of metalloproteinase-1 (TIMP-1) imbalance and the reduced anti-oxidant activity in bronchoalveolar lavage (BAL) fluid. NEt-4IB suppressed PPE-induced vascular endothelial growth factor (VEGF) expression in the airway. Treatment with NEt-4IB and bexarotene significantly suppressed the increase in static lung compliance and emphysematous changes. However, adverse effects of RXR agonists, including hypertriglyceridemia and hepatomegaly, were observed in bexarotene-treated mice but not in NEt-4IB-treated mice. CONCLUSION: These data suggest that RXRs play crucial roles in emphysema and airway inflammation, and novel partial RXR agonists could be potential therapeutic strategies for the treatment of PPE- and CSE-induced emphysema.


Asunto(s)
Enfisema Pulmonar/tratamiento farmacológico , Enfisema Pulmonar/metabolismo , Receptores X Retinoide/agonistas , Receptores X Retinoide/metabolismo , Animales , Bexaroteno/farmacología , Bexaroteno/uso terapéutico , Fumar Cigarrillos/efectos adversos , Femenino , Inflamación/inducido químicamente , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Ratones , Ratones Endogámicos BALB C , Enfisema Pulmonar/inducido químicamente
10.
Am J Physiol Lung Cell Mol Physiol ; 316(3): L407-L417, 2019 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-30604629

RESUMEN

Neuropeptide Y (NPY) is a neurotransmitter that is widely expressed in the brain and peripheral nervous system. Various immune cells express the NPY Y1 receptor. NPY modulates these cells via its Y1 receptor; however, involvement of NPY in the pathophysiology of bronchial asthma, particularly airway hyperresponsiveness (AHR), has not been defined. NPY-deficient and wild-type mice were intranasally sensitized and challenged to house dust mite (HDM) extract, and airway responses were monitored. After sensitization and challenge, NPY-deficient mice showed significantly lower AHR than wild-type mice, and numbers of eosinophils and levels of type 2 cytokines [interleukin (IL)-4, IL-5, and IL-13] in bronchoalveolar lavage fluid were significantly lower. Type 2 cytokine production from splenic mononuclear cells of HDM-sensitized mice was also significantly lower in NPY-deficient mice. Flow cytometry analysis showed that the number of CD4 T cells and CD11c+ antigen-presenting cells (APCs) was significantly lower in the lungs of NPY-deficient mice than in wild-type mice following sensitization and challenge. Significantly fewer CD11c+ APCs phagocytosed HDM in the mediastinal lymph nodes of NPY-deficient mice than in those of wild-type mice. Treatment with BIBO-3304, a NPY receptor antagonist, significantly suppressed development of HDM-induced AHR and inflammation in wild-type mice. These data identify an important contribution of NPY to allergen-induced AHR and inflammation through accumulation of dendritic cells in the airway and promotion of the type 2 immune response. Thus, manipulating NPY represents a novel therapeutic target to control allergic airway responses.


Asunto(s)
Células Dendríticas/metabolismo , Inflamación/patología , Pulmón/patología , Neuropéptido Y/metabolismo , Hipersensibilidad Respiratoria/metabolismo , Animales , Líquido del Lavado Bronquioalveolar/inmunología , Citocinas/metabolismo , Células Dendríticas/inmunología , Eosinófilos/inmunología , Hipersensibilidad/patología , Inflamación/genética , Ratones Transgénicos , Neuropéptido Y/genética , Hipersensibilidad Respiratoria/patología
11.
Arerugi ; 67(9): 1248-1256, 2018.
Artículo en Japonés | MEDLINE | ID: mdl-30464079
13.
Acta Med Okayama ; 71(5): 453-457, 2017 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-29042706

RESUMEN

Although recent retrospective studies suggested that the use of ß-blockers appears to help improve the mortality rate and decrease the rate of exacerbation in chronic obstructive pulmonary disease (COPD) patients with heart failure, the effects of ß-blockers on COPD patients without heart failure have not been established. Based on previous reports, we have launched a multicenter, prospective, single-arm phase II study to evaluate the preventive effect of the cardioselective ß-blocker bisoprolol in COPD exacerbation, in Japanese individuals with moderate-to-severe COPD who do not have heart failure but do have hypertension requiring the use of medication. The primary endpoint is the rate of mild-to-severe COPD exacerbation. The results of this study will clarify whether bisoprolol can prevent exacerbation in COPD patients without heart failure.


Asunto(s)
Bisoprolol/uso terapéutico , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Simpaticolíticos/uso terapéutico , Antihipertensivos/uso terapéutico , Estudios Clínicos como Asunto , Humanos , Hipertensión/tratamiento farmacológico , Japón/epidemiología , Enfermedad Pulmonar Obstructiva Crónica/epidemiología
14.
Int J Chron Obstruct Pulmon Dis ; 12: 1119-1124, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28435245

RESUMEN

BACKGROUND: Some recent studies have suggested that beta-blocker use in patients with chronic obstructive pulmonary disease (COPD) is associated with a reduction in the frequency of acute exacerbations. However, the long-term effects of beta-blocker use on lung function of COPD patients have hardly been evaluated. PATIENTS AND METHODS: We retrospectively reviewed 31 Japanese COPD patients taking beta-blockers for >1 year and 72 patients not taking them. The association between beta-blocker use and the annual change in forced expiratory volume in 1 second (FEV1) was assessed. RESULTS: At baseline, patient demographic characteristics were as follows: 97 males (mean age 67.0±8.2 years); 32 current smokers; and Global Initiative for Chronic Obstructive Lung disease (GOLD) stages I: n=26, II: n=52, III: n=19, and IV: n=6. Patients taking beta-blockers exhibited a significantly lower forced vital capacity (FVC), FEV1, and %FVC, and a more advanced GOLD stage. The mean duration of beta-blocker administration was 2.8±1.7 years. There were no differences in the annual change in FEV1 between patients who did and did not use beta-blockers (-7.6±93.5 mL/year vs -4.7±118.9 mL/year, P=0.671). After controlling for relevant confounders in multivariate analyses, it was found that beta-blocker use was not significantly associated with the annual decline in FEV1 (ß=-0.019; 95% confidence interval: -0.073 to 0.036; P=0.503). CONCLUSION: Long-term beta-blocker use in Japanese COPD patients might not affect the FEV1, one of the most important parameters of lung function in COPD patients.


Asunto(s)
Antagonistas Adrenérgicos beta/uso terapéutico , Enfermedades Cardiovasculares/tratamiento farmacológico , Pulmón/efectos de los fármacos , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Antagonistas Adrenérgicos beta/efectos adversos , Anciano , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/fisiopatología , Distribución de Chi-Cuadrado , Comorbilidad , Progresión de la Enfermedad , Femenino , Volumen Espiratorio Forzado , Humanos , Japón/epidemiología , Modelos Lineales , Pulmón/fisiopatología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Polifarmacia , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Capacidad Vital
15.
Intern Med ; 56(5): 551-555, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28250304

RESUMEN

We herein report the case of a 44-year-old man who was diagnosed with pneumocystis pneumonia (PCP) concomitant with ectopic adrenocorticotropic hormone (ACTH) syndrome, which had been caused by a large cell neuroendocrine carcinoma of the thymus. Chest computed tomography revealed ground-glass opacities in the lungs. PCP was diagnosed by a polymerase chain reaction with bronchoalveolar lavage. The levels of cortisol were slowly corrected with an adrenal enzyme inhibitor, and the exacerbation of PCP was successfully avoided. Our case indicates that in addition to prophylaxis, the early diagnosis of PCP and the slow correction of hypercortisolemia should be considered in order to prevent an exacerbation due to the reconstitution of the immune function in patients with ectopic ACTH syndrome.


Asunto(s)
Síndrome de ACTH Ectópico/complicaciones , Carcinoma Neuroendocrino/complicaciones , Infecciones Oportunistas/complicaciones , Neumonía por Pneumocystis/complicaciones , Neoplasias del Timo/complicaciones , Síndrome de ACTH Ectópico/tratamiento farmacológico , Adulto , Lavado Broncoalveolar , Diagnóstico Precoz , Inhibidores Enzimáticos/uso terapéutico , Humanos , Hidrocortisona/sangre , Masculino , Metirapona/uso terapéutico , Infecciones Oportunistas/diagnóstico , Neumonía por Pneumocystis/diagnóstico , Tomografía Computarizada por Rayos X
16.
Respir Res ; 18(1): 23, 2017 01 23.
Artículo en Inglés | MEDLINE | ID: mdl-28114934

RESUMEN

BACKGROUND: Retinoid X receptors (RXRs) are members of the nuclear receptor (NR) superfamily that mediate signaling by 9-cis retinoic acid, a vitamin A (retinol) derivative. RXRs play key roles not only as homodimers but also as heterodimeric partners-e.g., retinoic acid receptors (RARs), vitamin D receptors (VDRs), liver X receptors (LXRs), and peroxisome proliferator-activated receptors (PPARs). The NR family was recently associated with allergic diseases, but the role of RXRs in allergen-induced airway responses is not well defined. The goal of this study is to elucidate the role of RXRs in asthma pathogenesis and the potency of RXR partial agonist in the treatment of allergic airway inflammation and airway hyperresponsiveness using a murine model of asthma. METHODS: We investigated the effect of a novel RXR partial agonist (NEt-4IB) on the development of allergic airway inflammation and airway hyperresponsiveness (AHR) in a murine model of asthma. Balb/c mice were sensitized (days 0 and 14) and challenged (days 28-30) with ovalbumin (OVA), and airway inflammation and airway responses were monitored 48 h after the last OVA challenge. NEt-4IB was administered orally on days 25 to 32. RESULTS: Oral administration of NEt-4IB significantly suppressed AHR and inflammatory cell accumulation in the airways and attenuated the levels of TNF-α in the lung and IL-5, IL-13 and NO levels in bronchoalveolar lavage (BAL) fluid and the number of periodic acid Schiff (PAS)-positive goblet cells in lung tissue. Treatment with NEt-4IB also significantly suppressed NF-κB expression. CONCLUSION: These data suggest that RXRs may be of crucial importance in the mechanism of allergic asthma and that the novel RXR partial agonist NEt-4IB may be a promising candidate for the treatment of allergic airway inflammation and airway hyperresponsiveness in a model of allergic asthma.


Asunto(s)
Asma/tratamiento farmacológico , Asma/inmunología , Hiperreactividad Bronquial/tratamiento farmacológico , Hiperreactividad Bronquial/inmunología , Neumonía/tratamiento farmacológico , Neumonía/inmunología , Receptores X Retinoide/inmunología , Animales , Antiasmáticos/administración & dosificación , Femenino , Ratones , Ratones Endogámicos BALB C , Receptores X Retinoide/agonistas , Resultado del Tratamiento
17.
Acta Med Okayama ; 70(4): 273-7, 2016 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27549672

RESUMEN

Heerfordt's syndrome is a rare manifestation of sarcoidosis and is defined as a combination of facial palsy, parotid swelling, and uveitis, associated with a low-grade fever. We report a case of Heerfordt's syndrome presenting with a high fever and increased serum tumor necrosis factor alpha (TNF-α) levels. The patient had facial palsy, parotid swelling, uveitis, and swelling of the right supraclavicular and hilar lymph nodes. Corticosteroid therapy was initiated, and her symptoms soon resolved completely, in tandem with a decrease in TNF-α serum levels.


Asunto(s)
Fiebre/complicaciones , Factor de Necrosis Tumoral alfa/sangre , Fiebre Uveoparotidea/sangre , Fiebre Uveoparotidea/patología , Adulto , Femenino , Glucocorticoides/uso terapéutico , Humanos , Prednisolona/uso terapéutico , Fiebre Uveoparotidea/tratamiento farmacológico
18.
Am J Respir Cell Mol Biol ; 55(5): 697-707, 2016 11.
Artículo en Inglés | MEDLINE | ID: mdl-27351934

RESUMEN

We recently reported that IL-17A plays a critical role in the development of porcine pancreatic elastase (PPE)-induced emphysema. The proliferation of T-helper type 17 (Th17) cells was induced by IL-23. To determine the contribution of IL-23 to the development of pulmonary emphysema, a mouse model of PPE-induced emphysema was used in which responses of IL-23p19-deficient (IL-23-/-) and wild-type (WT) mice were compared. Intratracheal instillation of PPE induced emphysematous changes in the lungs and was associated with increased levels of IL-23 in lung homogenates. Compared with WT mice, IL-23-/- mice developed significantly lower static compliance values and markedly reduced emphysematous changes on histological analyses after PPE instillation. These changes were associated with lower levels of IL-17A and fewer Th17 cells in the lung. The neutrophilia seen in bronchoalveolar lavage fluid of WT mice was attenuated in IL-23-/- mice, and the reduction was associated with decreased levels of keratinocyte-derived cytokine and macrophage inflammatory protein-2 in bronchoalveolar lavage fluid. Treatment with anti-IL-23p40 monoclonal antibody significantly attenuated PPE-induced emphysematous changes in the lungs of WT mice. These data identify the important contributions of IL-23 to the development of elastase-induced pulmonary inflammation and emphysema, mediated through an IL-23/IL-17 pathway. Targeting IL-23 in emphysema is a potential therapeutic strategy for delaying disease progression.


Asunto(s)
Interleucina-23/metabolismo , Neumonía/inducido químicamente , Neumonía/metabolismo , Enfisema Pulmonar/inducido químicamente , Enfisema Pulmonar/metabolismo , Animales , Anticuerpos Monoclonales/farmacología , Líquido del Lavado Bronquioalveolar/citología , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD4-Positivos/metabolismo , Quimiocinas/metabolismo , Progresión de la Enfermedad , Interferón gamma/metabolismo , Interleucina-17/metabolismo , Interleucina-23/deficiencia , Cinética , Pulmón/patología , Recuento de Linfocitos , Ratones Endogámicos C57BL , Elastasa Pancreática , Neumonía/complicaciones , Neumonía/patología , Enfisema Pulmonar/complicaciones , Enfisema Pulmonar/patología , Sus scrofa
19.
Arerugi ; 64(8): 1117-26, 2015 Aug.
Artículo en Japonés | MEDLINE | ID: mdl-26522413
20.
Am J Physiol Lung Cell Mol Physiol ; 309(8): L789-800, 2015 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-26472810

RESUMEN

The receptor for advanced glycation end-products (RAGE) is a multiligand receptor that belongs to the immunoglobulin superfamily. RAGE is reported to be involved in various inflammatory disorders; however, studies that address the role of RAGE in allergic airway disease are inconclusive. RAGE-sufficient (RAGE+/+) and RAGE-deficient (RAGE-/-) mice were sensitized to ovalbumin, and airway responses were monitored after ovalbumin challenge. RAGE-/- mice showed reduced eosinophilic inflammation and goblet cell metaplasia, lower T helper type 2 (Th2) cytokine production from spleen and peribronchial lymph node mononuclear cells, and lower numbers of group 2 innate lymphoid cells in the lung compared with RAGE+/+ mice following sensitization and challenge. Experiments using irradiated, chimeric mice showed that the mice expressing RAGE on radio-resistant structural cells but not hematopoietic cells developed allergic airway inflammation; however, the mice expressing RAGE on hematopoietic cells but not structural cells showed reduced airway inflammation. In contrast, absence of RAGE expression on structural cells enhanced innate airway hyperresponsiveness (AHR). In the absence of RAGE, increased interleukin (IL)-33 levels in the lung were detected, and blockade of IL-33 receptor ST2 suppressed innate AHR in RAGE-/- mice. These data identify the importance of RAGE expressed on lung structural cells in the development of allergic airway inflammation, T helper type 2 cell activation, and group 2 innate lymphoid cell accumulation in the airways. RAGE on lung structural cells also regulated innate AHR, likely through the IL-33-ST2 pathway. Thus manipulating RAGE represents a novel therapeutic target in controlling allergic airway responses.


Asunto(s)
Asma/etiología , Receptor para Productos Finales de Glicación Avanzada/fisiología , Hipersensibilidad Respiratoria/etiología , Alérgenos/administración & dosificación , Animales , Asma/patología , Asma/fisiopatología , Líquido del Lavado Bronquioalveolar/inmunología , Citocinas/metabolismo , Modelos Animales de Enfermedad , Femenino , Proteína 1 Similar al Receptor de Interleucina-1 , Ratones , Ratones de la Cepa 129 , Ratones Endogámicos C57BL , Ratones Noqueados , Ovalbúmina/administración & dosificación , Ovalbúmina/inmunología , Receptor para Productos Finales de Glicación Avanzada/deficiencia , Receptor para Productos Finales de Glicación Avanzada/genética , Receptores de Interleucina/antagonistas & inhibidores , Hipersensibilidad Respiratoria/patología , Hipersensibilidad Respiratoria/fisiopatología , Células Th2/inmunología
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA