Down-regulation of 8-oxoguanine DNA glycosylase 1 expression in the airway epithelium ameliorates allergic lung inflammation.
Down-regulation of 8-oxoguanine DNA glycosylase 1 expression in the airway epithelium ameliorates allergic lung inflammation.
复制标题
气道上皮中的8-氧气DNA糖基酶1表达的下调可改善过敏性肺部炎症。
DOI：
10.1016/j.dnarep.2012.10.002
复制
发表时间：
2013-01-01
期刊：
影响因子：
3.8
通讯作者：
Boldogh, Istvan
中科院分区：
文献类型：
--
作者：
Bacsi, Attila;Aguilera-Aguirre, Leopoldo;Szczesny, Bartosz;Radak, Zsolt;Hazra, Tapas K.;Sur, Sanjiv;Ba, Xueqing;Boldogh, Istvan
关键词：
Allergic airway inflammation is characterized by increased expression of pro-inflammatory mediators, inflammatory cell infiltration, mucus hypersecretion, and airway hyperresponsiveness, in parallel with oxidative DNA base and strand damage, whose etiological role is not understood. Our goal was to establish the role of 8-oxoguanine (8-oxoG), a common oxidatively damaged base, and its repair by 8-oxoguanine DNA glycosylase 1 (Ogg1) in allergic airway inflammatory processes. Airway inflammation was induced by intranasally administered ragweed (Ambrosia artemisiifolia) pollen grain extract (RWPE) in sensitized BALB/c mice. We utilized siRNA technology to deplete Ogg1 from airway epithelium; 8-oxoG and DNA strand break levels were quantified by Comet assays. Inflammatory cell infiltration and epithelial methaplasia were determined histologically, mucus and cytokines levels biochemically and enhanced pause was used as the main index of airway hyperresponsiveness. Decreased Ogg1 expression and thereby 8-oxoG repair in the airway epithelium conveyed a lower inflammatory response after RWPE challenge of sensitized mice, as determined by expression of Th2 cytokines, eosinophilia, epithelial methaplasia, and airway hyperresponsiveness. In contrast, 8-oxoG repair in Ogg1-proficient airway epithelium was coupled to an increase in DNA single-strand break (SSB) levels and exacerbation of allergen challenge-dependent inflammation. Decreased expression of the Nei-like glycosylases Neil1 and Neil2 that preferentially excise ring-opened purines and 5-hydroxyuracil, respectively, did not alter the above parameters of allergic immune responses to RWPE. These results show that DNA SSBs formed during Ogg1-mediated repair of 8-oxoG augment antigen-driven allergic immune responses. A transient modulation of OGG1 expression/activity in airway epithelial cells could have clinical benefits.
登录
查看更多内容
影响因子：
4.4
作者：
Csillag, Aniko;Boldogh, Istvan;Bacsi, Attila
通讯作者：
Bacsi, Attila
影响因子：
7.4
作者：
Bacsi, A;Kannan, S;Boldogh, I
通讯作者：
Boldogh, I
影响因子：
2.7
作者：
Gungor, Nejla;Haegens, Astrid;van Schooten, Frederik J.
通讯作者：
van Schooten, Frederik J.
影响因子：
5.3
作者：
Bacsi, Attila;Chodaczek, Grzegorz;Boldogh, Istvan
通讯作者：
Boldogh, Istvan
影响因子：
14.2
作者：
Bacsi, Attila;Choudhury, Barun K.;Boldogh, Istvan
通讯作者：
Boldogh, Istvan