title: 8-Oxoguanine-DNA glycosylase 1 deficiency modifies allergic airway inflammation by regulating STAT6 and IL-4 in cells and in mice.
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.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of North Dakota, Grand Forks, ND 58203-9037, USA.
authors.forename: Guoping
authors.initials: G
authors.lastname: Li
authors.forename: Kefei
authors.initials: K
authors.lastname: Yuan
authors.forename: Chunguang
authors.initials: C
authors.lastname: Yan
authors.forename: John
authors.initials: J
authors.lastname: Fox
authors.forename: Madeleine
authors.initials: M
authors.lastname: Gaid
authors.forename: Wayne
authors.initials: W
authors.lastname: Breitwieser
authors.forename: Arvind K
authors.initials: AK
authors.lastname: Bansal
authors.forename: Huawei
authors.initials: H
authors.lastname: Zeng
authors.forename: Hongwei
authors.initials: H
authors.lastname: Gao
authors.forename: Min
authors.initials: M
authors.lastname: Wu
mesh_terms: D000818:Animals; D001249:Asthma / Q000139:chemically induced / Q000201:enzymology / Q000473:pathology*; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D045647:DNA Glycosylases / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D004260:DNA Repair; D004847:Epithelial Cells / Q000201:enzymology / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced / Q000201:enzymology* / Q000276:immunology; D015847:Interleukin-4 / Q000378:metabolism*; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016328:NF-kappa B / Q000378:metabolism; D010047:Ovalbumin; D018384:Oxidative Stress; D010766:Phosphorylation; D039981:Pyroglyphidae / Q000276:immunology; D011897:Random Allocation; D017382:Reactive Oxygen Species / Q000378:metabolism; D050800:STAT6 Transcription Factor / Q000378:metabolism*; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D016207:Cytokines; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D017392:Thiobarbituric Acid Reactive Substances; D015847:Interleukin-4; D010047:Ovalbumin; D045647:DNA Glycosylases; C485990:Ogg1 protein, mouse
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