8-Oxoguanine-DNA glycosylase 1 deficiency modifies allergic airway inflammation by regulating STAT6 and IL-4 in cells and in mice

8-氧鸟嘌呤-DNA糖基化酶1缺乏通过调节细胞和小鼠中的STAT6和IL-4来改变过敏性气道炎症

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作者:Guoping Li, Kefei Yuan, Chunguang Yan, John Fox 3rd, Madeleine Gaid, Wayne Breitwieser, Arvind K Bansal, Huawei Zeng, Hongwei Gao, Min Wu

Abstract

8-Oxoguanine-DNA glycosylase (OGG-1) is a base excision DNA repair enzyme; however, its function in modulating allergic diseases remains undefined. Using OGG-1 knockout (KO) mice, we show that this protein affects allergic airway inflammation after sensitization and challenge by ovalbumin(OVA). OGG-1 KO mice exhibited less inflammatory cell infiltration and reduced oxidative stress in the lungs after OVA challenge compared to WT mice. The KO phenotype included decreased IL-4, IL-6, IL-10, and IL-17 in lung tissues. In addition, OGG-1 KO mice showed decreased expression and phosphorylation of STAT6 as well as NF-κB. Down-regulation of OGG-1 by siRNA lowered ROS and IL-4 levels but increased IFN-γ production in cultured epithelial cells after exposure to house dust mite extracts. OGG-1 may affect the levels of oxidative stress and proinflammatory cytokines during asthmatic conditions. OGG-1 deficiency negatively regulates allergen-induced airway inflammatory response.

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