期刊
BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH
卷 48, 期 7, 页码 654-664出版社
ASSOC BRAS DIVULG CIENTIFICA
DOI: 10.1590/1414-431X20154271
关键词
1,25-Dihydroxyvitamin D3; Asthma; Acetylation; Deacetylation; Histone deacetylase 2; NF-kappa B
资金
- Science and Technology Fund of Shanghai Jiatong University School of Medicine, China
Recent evidence indicates that a deficiency of 1,25-dihydroxyvitamin D-3 (1,25[OH](2)D-3) 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)(2)D-3 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)(2)D-3 pretreatment, 1,25(OH)(2)D-3 treatment, Dx treatment, and Dx and 1,25(OH)(2)D-3 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-kappa B) 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)(2)D-3 reduced the airway inflammatory response and the level of inflammatory cytokines in BAL. Although NF-kappa B p65 expression was attenuated in the pretreatment and treatment groups, the expression and enzyme activity of HDAC2 were increased. In addition, 1,25(OH)(2)D-3 and Dx had synergistic effects on the suppression of total cell infusion, cytokine release, and NF-kappa B p65 expression, and they also increased HDAC2 expression and activity in OVA/OVA rats. Collectively, our results indicated that 1,25(OH)(2)D-3 might be useful as a novel HDAC2 activator in the treatment of asthma.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据