ABSTRACT
Recent evidence indicates that a deficiency of 1,25-dihydroxyvitamin D3 (1,25[OH]2D3) may influence asthma pathogenesis; however, its roles in regulating specific molecular transcription mechanisms remain unclear. We aimed to investigate the effect of 1,25(OH)2D3 on the expression and enzyme activity of histone deacetylase 2 (HDAC2) and its synergistic effects with dexamethasone (Dx) in the inhibition of inflammatory cytokine secretion in a rat asthma model. Healthy Wistar rats were randomly divided into 6 groups: control, asthma, 1,25(OH)2D3 pretreatment, 1,25(OH)2D3 treatment, Dx treatment, and Dx and 1,25(OH)2D3 treatment. Pulmonary inflammation was induced by ovalbumin (OVA) sensitization and challenge (OVA/OVA). Inflammatory cells and cytokines in the bronchoalveolar lavage (BAL) fluid and histological changes in lung tissue were examined. Nuclear factor kappa B (NF-κB) p65 and HDAC2 expression levels were assessed with Western blot analyses and quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR). Enzyme activity measurements and immunohistochemical detection of HDAC2 were also performed. Our data demonstrated that 1,25(OH)2D3 reduced the airway inflammatory response and the level of inflammatory cytokines in BAL. Although NF-κB p65 expression was attenuated in the pretreatment and treatment groups, the expression and enzyme activity of HDAC2 were increased. In addition, 1,25(OH)2D3 and Dx had synergistic effects on the suppression of total cell infusion, cytokine release, and NF-κB p65 expression, and they also increased HDAC2 expression and activity in OVA/OVA rats. Collectively, our results indicated that 1,25(OH)2D3 might be useful as a novel HDAC2 activator in the treatment of asthma.
Subject(s)
Animals , Male , Asthma/drug therapy , Calcitriol/pharmacology , /drug effects , NF-kappa B/drug effects , Vitamins/pharmacology , Asthma/chemically induced , Blotting, Western , Bronchoalveolar Lavage Fluid/chemistry , Cell Count , Calcitriol/therapeutic use , Cytokines/analysis , Cytokines/drug effects , Disease Models, Animal , Enzyme-Linked Immunosorbent Assay , Gene Expression Regulation, Enzymologic/drug effects , /metabolism , Immunohistochemistry , Lung/chemistry , Lung/drug effects , NF-kappa B/analysis , Ovalbumin , Rats, Wistar , Real-Time Polymerase Chain Reaction , Reproducibility of Results , Treatment Outcome , Vitamins/therapeutic useABSTRACT
En China, las altiplanicies de Qinghai en el Tibet son las más altas del mundo, y en ellas residen los tibetianos nativos y los inmigrantes chinos (Han). Este artículo se ocupa de las enfermedades producidas por la altura. Existen tres problemas serios producidos por la altura. Primero, el edema pulmonar de altura (HAPE); se observa una alta incidencia de HAPE en los recién llegados a la altura, y por el contrario una menor incidencia en los nativos de altura que reascienden a ella, lo que difiere con los reportes en Norte América y en los Andes. Segundo, la enfermedad cardiaca de altura (HAHD). Los niños y los infantes son los que se encuentran especialmente en riesgo. La mayoría de infantes afectados por esta enfermedad son de origen Han, y presentan insuficiencia cardiaca congestiva severa debido a hipertension pulmonar dentro de los pocos meses de nacido o de arribo a la altura. Las autopsias muestran una hipertrofia ventricular derecha y un engrosamiento de la muscular de las arterias pulmonares periféricas. La mortalidad en promedio fue de 15 por ciento, tal que la HAHD infantil es una emfermedad fatal. Tercero, la enfermedad de Monge o mal de Montaña Crónico (CMS). En los indígenas tibetianos se han observado 15 casos de CMS entre 1991-1993. Los datos epidemiológicos y clínicos muestran que la CMS existe en la altiplanicie de Qinghai-Tibet.