Enhanced expression of urocortin in lung tissues of rats with allergic asthma.
Enhanced expression of urocortin in lung tissues of rats with allergic asthma.
复制标题
过敏性哮喘大鼠肺组织中尿皮质素表达增强。
DOI：
10.1016/j.bbrc.2005.12.214
复制
发表时间：
2006-03
影响因子：
3.1
通讯作者：
中科院分区：
文献类型：
--
作者：
支气管哮喘是一种以包括肥大细胞在内的多种炎症细胞持续活化为特征的慢性气道炎症性疾病。尿皮质素（Urocortin，UCN）是由肥大细胞合成和分泌的，活化的肥大细胞释放更多的UCN。另一方面，UCN可诱导肥大细胞脱颗粒和多种促炎因子的产生。本研究的目的是检测UCN在过敏性哮喘大鼠肺组织中的表达。24只雄性SD大鼠随机分为正常对照组、哮喘模型组和地塞米松组。通过皮下注射卵清蛋白（OVA）主动致敏动物，并在致敏后2周用1%OVA气雾剂激发。UCN mRNA和肽在正常大鼠肺中均有表达。半定量逆转录聚合酶链反应（RT-PCR）检测到哮喘模型组大鼠气道内有大量炎症细胞浸润，尿皮质素（urocortin）mRNA表达明显上调，免疫组化和Western blot检测到urocortin多肽表达明显上调。与此相反，地塞米松治疗导致气道炎症和减轻气道炎性细胞浸润的显着改善，再加上显着降低尿皮质素的表达。回归分析显示，Urocortin表达与支气管肺泡灌洗液中炎性细胞数呈正相关（P<0.01）。在本研究中，我们首次证实UCN在大鼠肺局部产生，并在哮喘大鼠的炎症气道中表达更明显。糖皮质激素治疗显着减少UCN在哮喘肺组织中的产生。肺外周产生的UCN可能是过敏性哮喘大鼠气道炎症的局部自分泌和旁分泌免疫炎症介质。
Bronchial asthma is defined as a chronic airway inflammatory disease characterized by sustained activation of many inflammatory cells including mast cells. Urocortin (UCN) is synthesized and secreted by human mast cells and activated mast cells release more UCN. On the other hand, UCN can induce mast cell degranulation and generation of many proinflammatory factors. The purpose of this study was to examine the expression profile of UCN in rat lung with allergic asthma. Twenty-four male Sprague–Dawley rats were allocated to normal control, asthma model, and dexamethasone group, respectively. Animals were actively sensitized by subcutaneous injection of ovalbumin (OVA) and challenged by an aerosol of 1% OVA 2 weeks after sensitization. Both UCN mRNA and peptide were expressed in normal rat lungs. Rats in asthma model group developed severe infiltration of inflammatory cells and inflammation in airway, together with a significantly up-regulated expression of urocortin mRNA detected by semi-quantitative reverse transcriptase-polymerase chain reaction and peptide measured both by immunohistochemistry and Western blot analysis. In contrast, treatment with dexamethasone resulted in markedly ameliorated airway inflammation and alleviated airway inflammatory cell infiltration, coupled with a significantly decreased urocortin expression. Regression analysis revealed a positive correlation between urocortin expression and the number of inflammatory cells in bronchoalveolar lavage fluid (P<0.01). In the present study, we first demonstrated that UCN was locally produced in rat lungs and expressed more pronouncedly in inflammatory airway of asthmatic rats. Glucocorticoid treatment markedly reduced the production of UCN in asthmatic lung tissues. Peripherally produced UCN in lung may act as a possible local autocrine and paracrine immune-inflammatory mediator in inflammatory airway of allergic asthma rats.
登录
查看更多内容
影响因子：
56.9
作者：
KARALIS, K;SANO, H;CHROUSOS, GP
通讯作者：
CHROUSOS, GP
影响因子：
4.8
作者：
Kempuraj, D;Papadopoulou, NG;Theoharides, TC
通讯作者：
Theoharides, TC
影响因子：
4.8
作者：
Donaldson, CJ;Sutton, SW;Vale, WW
通讯作者：
Vale, WW
DOI：
10.1172/jci116150
发表时间：
1992-12
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
L. Crofford;H. Sano;K. Karalis;E. Webster;E. Goldmuntz;G. Chrousos;R. Wilder
通讯作者：
L. Crofford;H. Sano;K. Karalis;E. Webster;E. Goldmuntz;G. Chrousos;R. Wilder
影响因子：
2.5
作者：
Vijendra K. Singh;S. C. Leu
通讯作者：
Vijendra K. Singh;S. C. Leu