Prevention of airway inflammation with topical cream containing imiquimod and small interfering RNA for natriuretic peptide receptor.
Prevention of airway inflammation with topical cream containing imiquimod and small interfering RNA for natriuretic peptide receptor.
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DOI：
10.1186/1479-0556-6-7
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发表时间：
2008-02-15
期刊：
影响因子：
--
通讯作者：
Mohapatra, Shyam S
中科院分区：
文献类型：
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作者：
Wang, Xiaoqin;Xu, Weidong;Mohapatra, Shyam S
背景：哮喘是一种以可逆性气道阻塞、高反应性和慢性炎症为特征的复杂疾病。哮喘的主要药物治疗包括支气管扩张β 2受体激动剂和抗炎糖皮质激素;但这些药物并不针对疾病的主要原因，即致病性Th 2细胞的产生。我们以前报道过ANP受体NPRA缺陷小鼠的过敏性炎症减少。在这里，我们确定是否siRNA的利钠肽受体A（siNPRA）保护哮喘时transdermally.METHODS：咪喹莫特霜与壳聚糖纳米颗粒混合含有siRNA绿色指示剂（siGLO）或siNPRA被施加到小鼠的皮肤。通过荧光显微术确认siGLO的递送。结果：SiNPRA经皮给药的可行性得到证实，SiNPRA经皮给药后，小鼠气道高反应性、嗜酸性粒细胞增多、肺组织病理学改变和促炎细胞因子的变化均得到证实。在小鼠哮喘模型中，与对照组相比，用含有siNPRA壳聚糖纳米颗粒的咪喹莫特乳膏治疗的BALB/c小鼠显示出显著降低的气道高反应性、嗜酸性粒细胞增多、肺组织病理学和肺匀浆中的促炎细胞因子IL-4和IL-5。这些结果表明，含有咪喹莫特和siNPRA纳米颗粒的局部乳膏发挥抗肿瘤作用。可能为哮喘提供一种新的简单的治疗方法。
BACKGROUND: Asthma is a complex disease, characterized by reversible airway obstruction, hyperresponsiveness and chronic inflammation. Principle pharmacologic treatments for asthma include bronchodilating beta2-agonists and anti-inflammatory glucocorticosteroids; but these agents do not target the main cause of the disease, the generation of pathogenic Th2 cells. We previously reported reduction in allergic inflammation in mice deficient in the ANP receptor NPRA. Here we determined whether siRNA for natriuretic peptide receptor A (siNPRA) protected against asthma when administered transdermally.METHODS: Imiquimod cream mixed with chitosan nanoparticles containing either siRNA green indicator (siGLO) or siNPRA was applied to the skin of mice. Delivery of siGLO was confirmed by fluorescence microscopy. The anti-inflammatory activity of transdermal siNPRA was tested in OVA-sensitized mice by measuring airway hyperresponsiveness, eosinophilia, lung histopathology and pro-inflammatory cytokines.RESULTS: SiGLO appearing in the lung proved the feasibility of transdermal delivery. In a mouse asthma model, BALB/c mice treated with imiquimod cream containing siNPRA chitosan nanoparticles showed significantly reduced airway hyperresponsiveness, eosinophilia, lung histopathology and pro-inflammatory cytokines IL-4 and IL-5 in lung homogenates compared to controls.CONCLUSION: These results demonstrate that topical cream containing imiquimod and siNPRA nanoparticles exerts an anti-inflammatory effect and may provide a new and simple therapy for asthma.