Potential role for 8-oxoguanine DNA glycosylase in regulating inflammation

Mabley, JG; Pacher, P; Deb, A; Wallace, R; Elder, RH; Szabó, C

Abstract

OGG-1 DNA glycosylase (OGG-1) is an enzyme involved in DNA repair. It excises 7,8-dihydro-8-oxoguanine, which is formed by oxidative damage of guanine. We have investigated the role of OGG-1 in inflammation using three models of inflammation: endotoxic shock, diabetes, and contact hypersensitivity. We found that OGG-1(-/-) mice are resistant to endotoxin (lipopolysaccharide, LPS)-induced organ dysfunction, neutrophil infiltration and oxidative stress, when compared with the response seen in wild-type controls (OGG(+/+)). Furthermore, the deletion of the OGG-1 gene was associated with decreased serum cytokine and chemokine levels and prolonged survival after LPS treatment. Type I diabetes was induced by multiple low-dose streptozotocin treatment. OGG-1(-/-) mice were found to have significantly lower blood glucose levels and incidence of diabetes as compared with OGG-1(+/+) mice. Biochemical analysis of the pancreas showed that OGG-1(-/-) mice had greater insulin content, indicative of a greater beta-cell mass coupled with lower levels of the chemokine MIP-1alpha and Th1 cytokines IL-12 and TNF-alpha. Levels of protective Th2 cytokines, IL-4 and IL-10 were significantly higher in the pancreata of OGG-1(-/-) mice as compared with the levels measured in wild-type mice. In the contact hypersensitivity induced by oxazolone, the OGG-1(-/-) mice showed reduced neutrophil accumulation, chemokine, and Th1 and Th2 cytokine levels in the ear tissue. The current studies unveil a role for OGG-1 in the regulation of inflammation.

Citation

Mabley, J., Pacher, P., Deb, A., Wallace, R., Elder, R., & Szabó, C. (2005). Potential role for 8-oxoguanine DNA glycosylase in regulating inflammation. FASEB Journal, 19(2), 290-2. https://doi.org/10.1096/fj.04-2278fje

• Journal Article Type: Article
• Publication Date: Jan 1, 2005
• Deposit Date: Oct 6, 2011
• Journal: The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
• Print ISSN: 0892-6638
• Publisher: Federation of American Society of Experimental Biology
• Peer Reviewed: Peer Reviewed
• Volume: 19
• Issue: 2
• Pages: 290-2
• DOI: https://doi.org/10.1096/fj.04-2278fje
• Publisher URL: http://dx.doi.org/10.1096/fj.04-2278fje