RESUMEN
Plasmacytoid dendritic cells (pDCs) are critical in controlling adaptive immunity, but the mechanisms governing cytokine expression remain incompletely defined. Analogues of prostaglandin (PG)I(2), such as iloprost, can modulate functions of myeloid dendritic cells, but their involvement in the regulation of human pDCs remains unknown. To this end, the regulatory role of PGI(2) analogues on cytokine expression in pDCs was investigated. Circulating pDCs were magnetically sorted with BDCA-4 cell isolation kits from human peripheral blood mononuclear cells and treated with varying concentrations of iloprost with or without the addition of Toll-like receptor agonists, or an I prostanoid (IP) receptor antagonist, CAY10449. The levels of tumour necrosis factor (TNF)-alpha, interferon (IFN)-alpha and interleukin (IL)-10 were measured by ELISA. Iloprost induced IL-10 expression, but suppressed CpG oligodeoxynucleotide- (or imiquimod-) induced TNF-alpha and IFN-alpha production in pDCs. This effect was reversed by the addition of CAY10449. Forskolin, a cyclic adenosine monophosphate activator, conferred a similar modulating effect to that noted in iloprost-treated pDCs, although a higher concentration of forskolin was required to exert the same effect. Iloprost enhanced interleukin-10 and suppressed Toll-like receptor-mediated tumour necrosis factor-alpha and interferon-alpha production of human plasmacytoid dendritic cells via the I prostanoid receptor and, in part, the cyclic adenosine monophosphate pathway.
Asunto(s)
Citocinas/biosíntesis , Células Dendríticas/citología , Epoprostenol/análogos & derivados , Regulación de la Expresión Génica , Benzofenonas/farmacología , Colforsina/farmacología , AMP Cíclico/metabolismo , Ensayo de Inmunoadsorción Enzimática , Humanos , Iloprost/farmacología , Imidazoles/farmacología , Interferón-alfa/metabolismo , Interleucina-10/metabolismo , Oligonucleótidos/química , Inhibidores de Agregación Plaquetaria/farmacología , Transducción de Señal , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
It is unknown whether formoterol and salmeterol, two long-acting beta(2)-adrenoreceptor agonists, have regulatory functions in the production of T-helper cell (Th) type 2- and Th1-related chemokines by monocytes and bronchial epithelial cells. In the present study, the effects of formoterol and salmeterol on lipopolysaccharide (LPS)-induced expression of the Th2-related chemokine macrophage-derived chemokine (MDC; CCL22) and the Th1-related chemokine interferon-gamma-inducible protein (IP)-10 (CXCL10) were investigated in a monocytic cell line, THP-1, and in human primary monocytes. In addition, their effects on the expression of the Th2-related chemokine thymus- and activation-regulated chemokine (TARC; CCL17) were evaluated in an epithelial cell line, BEAS-2B. Formoterol enhanced MDC but suppressed IP-10 production in monocytes induced by LPS. Higher doses of salmeterol were required to enhance LPS-induced MDC expression in THP-1 cells. Formoterol and salmeterol could significantly suppress TARC expression in BEAS-2B cells. These effects could be reversed by a selective beta(2)-adrenoreceptor antagonist, ICI-118551. Formoterol- and LPS-induced MDC expression was inhibited by budesonide. Both long-acting beta(2)-adrenoreceptor agonists suppressed thymus- and activation-regulated chemokine expression in bronchial epithelial cells mediated via beta(2)-adrenoreceptors. Formoterol at physiological concentrations could suppress lipopolysaccharide-induced T-helper cell type 1-related chemokine (interferon-gamma-inducible protein-10) but enhance T-helper cell type 2-related chemokine (macrophage-derived chemokine) expression in human monocytes. Long-acting beta(2)-adrenoreceptor agonists may increase T-helper cell type 2-related chemokine expression in monocytes and T-helper cell type 2 recruitment and, therefore, long-acting beta(2)-adrenoreceptor agonist monotherapy may not be an appropriate therapeutic option for asthma.
Asunto(s)
Agonistas Adrenérgicos beta/farmacología , Albuterol/análogos & derivados , Quimiocinas/metabolismo , Células Epiteliales/efectos de los fármacos , Etanolaminas/farmacología , Macrófagos/efectos de los fármacos , Proteínas ADAM/metabolismo , Albuterol/farmacología , Bronquios/citología , Bronquios/efectos de los fármacos , Línea Celular , Quimiocina CCL17/metabolismo , Quimiocina CXCL10/metabolismo , Células Epiteliales/metabolismo , Fumarato de Formoterol , Humanos , Macrófagos/metabolismo , Xinafoato de Salmeterol , Células TH1/fisiología , Células Th2/fisiología , Proteínas Supresoras de Tumor/metabolismoRESUMEN
Breast cerebrospinal fluid pseudocysts are a rare complication of ventriculoperitoneal (VP) shunting. It is very unusual for the peritoneal catheter of a shunt to become wrapped around a prosthesis a previously augmented breast. Three previously reported patients developed an enlarging breast lump and were diagnosed with shunt migration around the prosthesis. Our patient underwent bilateral breast augmentation and subsequently a VP shunt. We observed on frequent follow-up chest X-rays performed for pneumonia and mechanical ventilation that the peritoneal catheter had gradually wrapped around her prosthesis. She developed a progressively enlarging breast lump which resolved with drainage of the cerebrospinal fluid collection and revision of the VP shunt.
Asunto(s)
Implantes de Mama/efectos adversos , Cateterismo/efectos adversos , Quistes/etiología , Derivación Ventriculoperitoneal/efectos adversos , Femenino , Migración de Cuerpo Extraño/fisiopatología , Humanos , Persona de Mediana Edad , Accidente Cerebrovascular/cirugíaRESUMEN
BACKGROUND: Asthma is a complex disorder, which is known to be affected by interactions between genetic and environmental factors. The human Eotaxin 1 and CCR3 attract eosinophils and Th2-lymphocytes to migrate to the inflammatory foci that could represent a key mechanism in allergy and asthma. OBJECTIVE: We hypothesized that Eotaxin1 gene Ala23Thr and A-384 G, and CCR3 gene T51C polymorphisms are associated with plasma Eotaxin levels and predispose individuals to asthma pathogenesis. METHODS: One hundred seventy-eight hospital-based asthmatic children and 277 community-based controls aged from 5 to 12 years were recruited in southern Taiwan. Whole blood samples and questionnaires were collected. In this study, we addressed genetic effects of Eotaxin 1 and CCR3 genes on asthma, plasma IgE and Eotaxin 1 levels. RESULTS: In comparison with subjects with Ala23Ala genotype, Ala23Thr polymorphism of the Eotaxin 1 gene showed a significant protective effect on asthma (AOR = 0.58, 95% CI = 0.37-0.92). We demonstrated that the mean Eotaxin 1 concentration was significantly higher in subjects with Ala23Ala than in subjects with Thr23Thr (P = 0.005) or Ala23Thr (P = 0.07), which showed a gene-dose dependent relationship. But, we observed that the A-384G polymorphism of Eotaxin 1 gene and T51C polymorphism of CCR3 gene are not associated with asthma. CONCLUSION: This study finding provide a strong evidence that Eotaxin 1 Thr23Thr homozygote has a protective effect on asthma and significantly decreases plasma Eotaxin 1 concentrations in asthmatics in Taiwan.
Asunto(s)
Asma/genética , Asma/inmunología , Quimiocina CCL11/sangre , Quimiocina CCL11/genética , Inmunoglobulina E/sangre , Polimorfismo Genético/genética , Receptores CCR3/genética , Niño , Preescolar , ADN/sangre , ADN/aislamiento & purificación , Eosinófilos/inmunología , Eosinófilos/metabolismo , Femenino , Frecuencia de los Genes/inmunología , Predisposición Genética a la Enfermedad/genética , Genotipo , Humanos , Masculino , Polimorfismo Genético/inmunología , Polimorfismo de Longitud del Fragmento de Restricción/genética , Polimorfismo de Longitud del Fragmento de Restricción/inmunología , Polimorfismo de Nucleótido Simple/genética , Polimorfismo de Nucleótido Simple/inmunología , Receptores CCR3/metabolismo , Valores de Referencia , Índice de Severidad de la Enfermedad , Linfocitos T/inmunología , Linfocitos T/metabolismo , TaiwánRESUMEN
BACKGROUND: Asthma is a multi-factorial disorder caused by complex interactions between genetic and environmental factors. IFN-gamma and IFN regulatory factor 1 (IRF-1) affect Th1/Th2 cytokine balance, and influence the differentiation of Th2 cells, which influence the development of asthma. OBJECTIVE: This study investigated CA repeats polymorphism of the IFN-gamma gene and GT repeats polymorphism of the IRF-1 gene, which may predispose individuals to asthma pathogenesis. METHODS: In the present study, we used the transmission/disequilibrium test (TDT) to investigate the relationship between asthma and the IFN-gamma and IRF-1 polymorphisms by studying 348 subjects composed of 232 parents and 116 asthmatic children. RESULTS: For global TDT test, IFN-gamma CA repeats and IRF-1 GT repeat polymorphisms showed a significant association with asthma in children (P=0.009 and 0.017, respectively). We demonstrated that 13 CA repeats (138 bp) of IFN-gamma gene and 11 GT repeats (306 bp) of IRF-1 gene are significantly preferentially transmitted to asthmatic children (T/NT=89/61, chi2=8.43, P<0.005 and T/NT=75/49, chi2=8.18, P<0.005, respectively). The offspring will have an increased risk of asthma when their parents transmit IFN-gamma 13 CA repeats (OR=1.83, P=0.009) and IRF1 11 GT repeats (OR=1.88, P=0.007) to them. But we observed that the IFN-gamma and IRF-1 polymorphisms are not associated with IgE concentrations. CONCLUSION: These findings provide strong evidence of which IFN-gamma CA repeat and IRF-1 GT repeat polymorphisms influence the risk of asthma for children in Taiwan.
Asunto(s)
Asma/genética , Factor 1 Regulador del Interferón/genética , Interferón gamma/genética , Polimorfismo Genético/genética , Adulto , Asma/sangre , Niño , Salud de la Familia , Femenino , Frecuencia de los Genes/genética , Predisposición Genética a la Enfermedad/genética , Humanos , Inmunoglobulina E/sangre , Desequilibrio de Ligamiento/genética , Masculino , Fenotipo , TaiwánRESUMEN
The impedance of the junction between a solid or aqueous electrolyte and a metal electrode at which no charge transfer processes occur (blocking contacts) follows closely the constant phase angle form, Z = A(j omega)-n, over a wide frequency range, where A is a constant, and the frequency exponent n is typically in the range of 0.7 to 0.95. Several models have been proposed in which the magnitude of the frequency exponent n is related by a simple expression to the fractal dimension d of the rough electrode surface. But experiments with aqueous H2SO4 and roughened platinum and silicon electrodes show that there is no simple relationship, if any at all, between n and d when d is determined from the analysis of one dimensional surface profiles. Moreover, n is not a simple function of the average roughness of the electrode. In order to gain some insight into the effect of electrode topography and the interface impedance, a model for the response of the interface to a constant voltage pulse was constructed. This model is based on the idea that, following a pulse, locally concentrated regions of ions accumulate rapidly at the tips of large protrusions on the electrode surface which screens deeper regions of the electrode from the field driven flux of mobile ions. After this rapid charging, ions are able to reach the deeper, screened regions of the electrode by diffusion, and it is this diffusive process that gives rise to the observed t1-n dependence of the charge collected. Computer simulations, similar to the diffusion limited aggregation model, using measured profiles as fixed (non-growing) clusters, gave exponents n in good agreement with experiment.
Asunto(s)
Simulación por Computador , Conductividad Eléctrica , Electrodos , Electrólitos/química , Modelos Teóricos , Propiedades de SuperficieRESUMEN
In this study, we demonstrate that type VI adenylyl cyclase (ACVI) is glycosylated in vivo. Treating HEK293 cells expressing ACVI with tunicamycin to block the addition of N-linked oligosaccharide or removing the N-linked oligosaccharide by in vitro peptidyl-N-glycosidase F digestion reduced the molecular mass of ACVI. Furthermore, tunicamycin treatment suppressed the forskolin-stimulated activity of ACVI. Mutation of either one or both potential N-glycosylation sites (Asn(805) and Asn(890), located on extracellular loops 5 and 6, respectively) also reduced the molecular mass of ACVI. Therefore, ACVI was glycosylated at both Asn(805) and Asn(890). Confocal analysis indicated that glycosylation was not required for the delivery of ACVI to the cell surface. Although no significant alterations in K(m) values for ATP or sensitivity to divalent cations were detected, the glycosylation-deficient ACVI mutant N805Q/N890Q-ACVI exhibited much lower forskolin-, Mn(2+)-, and Mg(2+)-stimulated cyclase activities than did wild-type ACVI. By contrast, the Galpha(s)-stimulated cyclase activities of wild-type ACVI and N805Q/N890Q-ACVI were indistinguishable. Furthermore, compared with wild-type ACVI, N805Q/N890Q-ACVI was less sensitive to inhibition mediated by dopamine D2 receptors or by protein kinase C. Collectively, glycosylation of ACVI not only affected its catalytic activity in an activator-dependent manner, but also altered its ability to be regulated by a Galpha(i) protein-coupled receptor or by protein kinase C.
Asunto(s)
Adenilil Ciclasas/metabolismo , Asparagina/metabolismo , Adenilil Ciclasas/química , Catálisis , Línea Celular , Glicosilación , Humanos , Inmunohistoquímica , Proteína Quinasa C/metabolismo , Proteínas Recombinantes/metabolismoRESUMEN
Pulmonary valvular stenosis (PS) with intact ventricular septum is a common congenital heart disease. In general, mild PS has a benign clinical course. However, in severe PS and some cases of moderate stenosis, increasing severity of the lesion may occur. The manifestations of either cerebrovascular accident (CVA) or congestive heart failure (CHF) are rarely reported in pediatric patients with PS. In this report, we describe a girl with severe PS complicated by seizures and sudden onset of hemiparesis at 13 months of age who developed CHF when 16 months old. CHF was cured after successful balloon valvuloplasty. She remained well without residual hemiparesis or recurrent seizures during the 1-year follow-up. Early balloon valvuloplasty should be emphasized in patients with severe PS, even if there are no significant clinical symptoms. With prompt balloon valvuloplasty, these complications can be effectively prevented.