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United States Department of Agriculture

Agricultural Research Service

Research Project: DIETARY MODULATION OF OBESITY-RELATED CANCER BY SELENIUM

Location: Dietary Prevention of Obesity-related Disease Research

Title: 8-oxoguanine DNA glycosylase 1-deficiency modifies allergic airway inflammation by regulating STAT6 and IL-4 in cells and in mice)

Author
item Li, Guo-ping
item Yuan, Kefei
item Fox, John
item Gaid, Madeline
item Seeger, Drew
item Weaver, Andrew
item Breitwieser, Wayne
item Bansal, Arvind
item Zeng, Huawei
item Gao, Hongwei
item Wu, Min

Submitted to: Free Radicals in Biology and Medicine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/12/2011
Publication Date: 1/5/2012
Citation: Li, G., Yuan, K., Fox, J., Gaid, M., Seeger, D., Weaver, A., Breitwieser, W., Bansal, A.K., Zeng, H., Gao, H., Wu, M. 2012. 8-oxoguanine DNA glycosylase 1-deficiency modifies allergic airway inflammation by regulating STAT6 and IL-4 in cells and in mice. Free Radicals in Biology and Medicine. 15;52(2):392-401.

Interpretive Summary: 8-oxoguanine-DNA glycosylase (OGG-1) is an enzyme involved in DNA repair. OGG-1 has a potential role in regulating inflammation but its function in modulating allergic diseases remains undefined. To investigate the role of OGG-1 in mediating allergic inflammation, we used OGG-1 knockout (KO) mice to determine the impact of OGG1-deficiency on allergic airway inflammation. OGG-1 KO mice and WT mice were sensitized and challenged by ovalbumin (OVA) or control. The lung tissues were assessed for general morphology and cellular infiltration. Cytokine levels, oxidative stress, and OGG-1 activity in lung tissue were determined. These findings indicate that OGG-1 acts as an immune regulator of allergic response. Thus, OGG-1-deficiency plays a negative regulatory role in allergen-induced airway inflammatory response, suggesting that OGG-1 may aggravate allergic inflammatory response. The information will be useful for scientists and health-care professionals who are interested in the prevention of allergic inflammation.

Technical Abstract: Background: 8-oxoguanine-DNA glycosylase (OGG-1) is an enzyme involved in DNA repair. OGG-1 has a potential role in regulating inflammation but its function in modulating allergic diseases remains undefined. Objectives: To investigate the role of OGG-1 in mediating allergic inflammation, we used OGG-1 knockout (KO) mice to determine the impact of OGG1-deficiency on allergic airway inflammation. Methods: OGG-1 KO mice and WT mice were sensitized and challenged by ovalbumin (OVA) or control. The lung tissues were assessed for general morphology and cellular infiltration. Cytokine levels, oxidative stress, and OGG-1 activity in lung tissue were determined. STAT1, STAT3, STAT6, and NF-'B were quantified by western blot and immunohistochemistry. MLE-12 cells were stimulated with house dust mite (HDM) extracts (an allergen causing asthmatic symptoms). Using siRNA to knockdown OGG-1 in epithelial cells, we determined the impact of OGG-1 on the production of reactive oxygen species (ROS), NF-'B and STAT6. Results: OGG-1 KO mice exhibited lower inflammatory cell infiltration and reduced oxidative stress in the lungs after ovalbumin (OVA)-challenge compared to WT mice. These phenotypes were associated with lowered production of Th1 cytokines (TNF-a, INF-', IL-2, and IL-12), Th2 cytokines (IL-4, IL-6, and IL-10) and IL-17 in lung tissues. OGG-1 KO mice also showed reduced STAT3 and STAT6 expression as well as reduced STAT1 and NF-'B phosphorylation by OVA-challenge. To further investigate the role of OGG-1 in lung epithelial cells, OGG-1 siRNA was introduced into cultured MLE-12 cells. Down-regulation of OGG-1 in lung epithelial cells exhibited lower ROS release, IL-4, IL-2, and IL-17 production, but higher INF-' production. In addition, STAT6 expression and NF-'B phosphorylation were decreased in HDM extract-treated OGG-1 knockdown epithelial cells. Conclusions: These novel findings indicate that OGG-1 acts as an immune regulator of allergic response. Thus, OGG-1-deficiency plays a negative regulatory role in allergen-induced airway inflammatory response, suggesting that OGG-1 may aggravate allergic inflammatory response.

Last Modified: 8/24/2016
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