IMIQUIMOD, A TOLL-LIKE RECEPTOR 7 LIGAND, INHIBITS AIRWAY REMODELLING IN A MURINE MODEL OF CHRONIC ASTHMA
IMIQUIMOD, A TOLL-LIKE RECEPTOR 7 LIGAND, INHIBITS AIRWAY REMODELLING IN A MURINE MODEL OF CHRONIC ASTHMA
复制标题
IMIQUIMOD 是一种 Toll 样受体 7 配体，可抑制慢性哮喘小鼠模型的气道重塑。
DOI：
10.1111/j.1440-1681.2008.05027.x
复制
发表时间：
2009-01-01
影响因子：
2.9
通讯作者：
Yin, Kai-Sheng
中科院分区：
文献类型：
--
作者：
Du, Qiang;Zhou, Lin-Fu;Yin, Kai-Sheng
咪喹莫特是一种合成toll样受体（TLR） 7配体，已被证明可减轻急性过敏性哮喘小鼠模型的气道炎症和气道高反应性（AHR）。在本研究中，我们研究了咪喹莫特对慢性实验性哮喘变应原诱导的气道重塑的影响。卵清蛋白（OVA）致敏小鼠长期雾化吸入OVA 8周。一些小鼠在虫卵攻击期间每天暴露于0.15%咪喹莫特气雾剂。在最后一次卵圆激发24小时后，评估小鼠气道炎症、AHR和气道重塑的发展情况。采用ELISA法和免疫组织化学法分别检测各组大鼠血清总IgE、支气管肺泡灌洗液（BALF）中Th2细胞因子（白细胞介素(IL)-4、IL-5、IL-13）水平和肺组织中转化生长因子(TGF)- β 1蛋白的表达。结果表明，咪喹莫特对慢性实验性哮喘的慢性炎症、持续性AHR和气道重构具有显著的抑制作用。此外，咪喹莫特降低了重塑气道中总血清IgE和BALF - Th2细胞因子水平，并降低了tgf - β 1的表达。总之，本研究结果表明，咪喹莫特可能减轻气道炎症和气道重构的进展，为哮喘的治疗提供了潜力。
Imiquimod, a synthetic Toll-like receptor (TLR) 7 ligand, has been shown to attenuate airway inflammation and airway hyperresponsiveness (AHR) in acute murine models of allergic asthma. In the present study, we investigated the effect of imiquimod on allergen-induced airway remodelling in chronic experimental asthma.Ovalbumin (OVA)-sensitized mice were chronically challenged with aerosolized OVA for 8 weeks. Some mice were exposed to an aerosol of 0.15% imiquimod daily during the period of OVA challenge. Twenty-four hours after the last OVA challenge, mice were evaluated for the development of airway inflammation, AHR and airway remodelling. The levels of total serum IgE and Th2 cytokines (interleukin (IL)-4, IL-5 and IL-13) in bronchoalveolar lavage fluid (BALF) and the expression of transforming growth factor (TGF)-beta 1 protein in lungs were measured by ELISA and immunohistochemistry, respectively.The results demonstrated that imiquimod significantly inhibited chronic inflammation, persistent AHR and airway remodelling in chronic experimental asthma. In addition, imiquimod reduced levels of total serum IgE and BALF Th2 cytokines and diminished expression of TGF-beta 1 in remodelled airways.In summary, the results of the present study indicate that imiquimod may attenuate the progression of airway inflammation and remodelling, providing potential in the treatment of asthma.