RESUMEN
BACKGROUND AND OBJECTIVE: Epidemiological studies have shown that the prevalence of adult asthma and severe asthma is higher in women. It has also been reported that female mice are more susceptible than males to the development of allergic airway inflammation and airway hyperresponsiveness (AHR). The influence of gender difference in the pathogenesis of severe asthma, especially airway remodelling in an animal model, has been studied rarely. We investigated gender difference in the development of airway remodelling using a long-term antigen-challenged mouse asthma model. METHODS: Following ovalbumin (OVA)/alum intraperitoneal injection, male or female mice (BALB/c) were challenged with aerosolized 1% OVA on 3 days/week for 5 weeks, and differences in AHR, airway inflammation and airway remodelling between the sexes were investigated. RESULTS: In OVA-sensitized and OVA-challenged (OVA/OVA) female mice, eosinophils, lymphocytes, T-helper type 2 cytokines and growth factors in bronchoalveolar lavage fluid were increased compared with OVA/OVA male mice. Histological features of airway remodelling were also increased in OVA/OVA female mice. Serum total and OVA-specific immunoglobulin E (IgE) and serum IgA were significantly elevated in OVA/OVA female mice. CONCLUSIONS: These results indicate that female mice experience more airway remodelling compared with male mice. These results suggest the involvement of sex hormones and gender differences in cellular functions in airway remodelling.
Asunto(s)
Remodelación de las Vías Aéreas (Respiratorias)/fisiología , Asma/metabolismo , Asma/fisiopatología , Inmunoglobulina A/metabolismo , Inmunoglobulina E/metabolismo , Inmunoglobulina G/metabolismo , Factores Sexuales , Animales , Asma/inducido químicamente , Quimiocinas/metabolismo , Citocinas/metabolismo , Modelos Animales de Enfermedad , Femenino , Hormonas Esteroides Gonadales/fisiología , Inyecciones Intraperitoneales , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Ovalbúmina/administración & dosificación , Ovalbúmina/efectos adversosRESUMEN
It has been pointed out that obesity is a risk factor for, and is involved in the exacerbation of asthma. Mounting evidence about adipose tissue-derived proteins (adipokines) gave rise to the current understanding of obesity as a systemic inflammatory disorder. In this review, we summarized the involvement of leptin, focusing on eosinophil functions. Several studies have indicated that leptin can restrain eosinophil apoptosis, enhance migration, increase adhesion molecules and induce cytokine production. Since leptin also acts on a variety of immune cells related to allergic response, increased leptin in obese individuals potentially explains the mechanism by which obesity leads to an exacerbation of asthma. Further studies targeting adipokines will delineate the association between obesity and eosinophil-associated diseases.
Asunto(s)
Eosinofilia/inmunología , Leptina/inmunología , Obesidad/inmunología , Tejido Adiposo/inmunología , Humanos , Inflamación/inmunología , Leptina/sangreRESUMEN
BACKGROUND: Tissue eosinophilia is one of the hallmarks of allergic diseases and Th2-type immune responses including asthma. Systemic inflammation caused by adipose tissue in obesity via production of adipokines such as leptin has been attracting attention recently as a contributor to exacerbation of allergic immune reactions. In this study, we examined whether leptin might affect eosinophil chemotactic responses. METHODS: Peripheral blood eosinophils were purified, and the effect of leptin on eosinophil migration was investigated using in vitro systems. RESULTS: High concentrations of leptin induced eosinophil chemotaxis and rapid phosphorylation of ERK1/2 and p38 mitogen-activated protein kinase but not calcium mobilization. We also found that pretreatment of eosinophils with physiological concentrations of leptin amplified the chemotactic responses to eotaxin. This leptin-primed chemotaxis appears to be associated with increased calcium mobilization but not with ERK1/2 and p38 pathways. CONCLUSIONS: These results indicate that leptin has both direct and indirect effects on eosinophil chemotaxis and intracellular signaling. In physiological settings, leptin may maintain eosinophil accumulation at allergic inflammatory foci.
Asunto(s)
Quimiocina CCL11/inmunología , Quimiocina CCL11/farmacología , Quimiotaxis de Leucocito , Eosinófilos/inmunología , Leptina/farmacología , Leptina/fisiología , Femenino , Humanos , Masculino , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Fosforilación , Proteínas Recombinantes/farmacología , Transducción de Señal , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
The T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) is a co-inhibitory receptor mainly expressed on T cells. Although TIGIT plays an important role in various autoimmune diseases, its role in atopic dermatitis (AD) remains unclear. In this study, we examined the expression levels of TIGIT and their association with clinical features in patients with AD. TIGIT expression on CD4+ T cells, central memory T cells, effector memory T cells and regulatory T cells was determined by flow cytometry. CD4+ T cells exhibited enhanced TIGIT expression in patients with AD compared with healthy individuals. In particular, effector memory T cells and regulatory T cells, but not central memory T cells, exhibited higher TIGIT expression in patients with AD than in healthy individuals. The frequency of TIGIT+ cells among CD4+ T cells was significantly increased in patients with mild AD compared with healthy individuals, while decreased in patients with severe AD. Consistently, the frequency of TIGIT+ cells among CD4+ T cells was negatively correlated with both serum thymus and activation-regulated chemokine levels and immunoglobulin E levels in patients with AD. Furthermore, TIGIT expression on CD4+ T cells inhibited cell proliferation in patients with AD. These results suggest that TIGIT expression on CD4+ T cells in patients with AD may be increased to suppress chronic cutaneous inflammation. Moreover, TIGIT expression may be impaired in a subset of patients with AD, leading to a deterioration of skin inflammation. Our study may provide new insight into a TIGIT pathway-based therapeutic approach for AD.
Asunto(s)
Linfocitos T CD4-Positivos/metabolismo , Dermatitis Atópica/inmunología , Receptores Inmunológicos/metabolismo , Adulto , Linfocitos T CD4-Positivos/inmunología , Estudios de Casos y Controles , Proliferación Celular , Quimiocina CCL17/sangre , Quimiocina CCL17/inmunología , Dermatitis Atópica/sangre , Femenino , Citometría de Flujo , Voluntarios Sanos , Humanos , Inmunoglobulina E/sangre , Inmunoglobulina E/inmunología , Masculino , Persona de Mediana Edad , Receptores Inmunológicos/inmunología , Piel/inmunologíaRESUMEN
Signaling through coinhibitory receptors downregulates the immune response to prevent excessive immune activation and maintain optimal immunity and tolerance. The aim of this study was to examine the levels of the soluble forms of coinhibitory receptors and their ligands, namely, galectin-9 (the ligand of T-cell immunoglobulin and mucin domain 3) and CD155 (the ligand of T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain), and their association with clinical features in patients with systemic sclerosis (SSc). The serum levels of galectin-9 and soluble sCD155 were examined by enzyme-linked immunosorbent assays in patients with SSc, and the results were evaluated with respect to clinical features. Patients with SSc exhibited raised serum levels of galectin-9, but not sCD155. Serum galectin-9 levels were raised not only in patients with diffuse cutaneous SSc but also in patients with limited cutaneous SSc. Furthermore, serum galectin-9 levels correlated positively with the erythrocyte sedimentation rate. In addition, increased serum galectin-9 levels tended to be associated with higher mortality and serious organ involvement. These results suggest that galectin-9, but not CD155, may be involved in the pathogenesis of SSc. In addition, the measurement of serum galectin-9 levels could be used to predict serious organ involvement and high mortality in patients with SSc.
Asunto(s)
Galectinas/sangre , Receptores Virales/sangre , Esclerodermia Sistémica/metabolismo , Piel/patología , Adolescente , Adulto , Anciano , Sedimentación Sanguínea , Niño , Humanos , Persona de Mediana Edad , Pronóstico , Esclerodermia Sistémica/diagnóstico , Esclerodermia Sistémica/mortalidad , Transducción de Señal , Análisis de Supervivencia , Adulto JovenAsunto(s)
Conducto Auditivo Externo/patología , Pérdida Auditiva Conductiva/tratamiento farmacológico , Hidroxicloroquina/uso terapéutico , Lupus Eritematoso Discoide/complicaciones , Piel/patología , Administración Oral , Anciano , Audiometría , Biopsia , Femenino , Pérdida Auditiva Conductiva/diagnóstico , Pérdida Auditiva Conductiva/etiología , Humanos , Lupus Eritematoso Discoide/tratamiento farmacológico , Lupus Eritematoso Discoide/patología , Resultado del TratamientoAsunto(s)
Antivirales/uso terapéutico , Fármacos Dermatológicos/uso terapéutico , Hepatitis C Crónica/tratamiento farmacológico , Psoriasis/tratamiento farmacológico , Ustekinumab/uso terapéutico , Anciano , Carbamatos , Hepacivirus/aislamiento & purificación , Hepatitis C Crónica/sangre , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/virología , Humanos , Imidazoles/uso terapéutico , Isoquinolinas/uso terapéutico , Masculino , Psoriasis/complicaciones , Psoriasis/diagnóstico , Pirrolidinas , ARN Viral/sangre , ARN Viral/aislamiento & purificación , Inducción de Remisión/métodos , Índice de Severidad de la Enfermedad , Sulfonamidas/uso terapéutico , Valina/análogos & derivadosRESUMEN
Pulmonary metastasis from leiomyosarcoma is rare and its clinical management is challenging. A single lung metastasis from a perineal leiomyosarcoma occurred in a 79-year-old woman. Five months after resection of the lung metastasis, a new metastatic tumor developed in the contralateral lung. Since the patient did not desire to receive hospitalized treatment, TS-1 (an oral agent consisting of a combination of tegafur, gimeracil, and oteracil potassium) therapy was started on an outpatient basis. The lung metastasis has been successfully controlled for at least 17 months with excellent tolerability. The clinical features and the treatment of this case are discussed.